首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1322954118091911646, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1322954116858782668, articleNumber=null, orderNo=null, doi=10.16016/j.2097-0927.202511049, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1762704000000, receivedDateStr=2025-11-10, revisedDate=1764259200000, revisedDateStr=2025-11-28, acceptedDate=null, acceptedDateStr=null, onlineDate=1793346441051, onlineDateStr=2026-10-30, pubDate=1767024000000, pubDateStr=2025-12-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793346441051, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793346441051, creator=13701087609, updateTime=1793346441051, updator=13701087609, issue=Issue{id=1322954116858782668, tenantId=1146029695717560320, journalId=1319373162502258839, year='2025', volume='47', issue='24', pageStart='3009', pageEnd='3159', issueExtLink='null', onlineDate='null', pubDate='1767024000000', pubDateStr='2025-12-30', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793346440757, creator='13701087609', updateTime=1793346440757, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=3009, endPage=3021, ext={EN=ArticleExt(id=1322954118326792671, articleId=1322954118091911646, tenantId=1146029695717560320, journalId=1319373162502258839, language=EN, title=High-salt diet promotes the progression of fibrosis in metabolic dysfunction-associated steatohepatitis via activating the PI3K/Akt/mTOR signaling pathway, columnId=1320434418116837551, journalTitle=Journal of Army Medical University, columnName=Basic Medicine, runingTitle=null, highlight=null, articleAbstract=
Objective

To explore the impact of high-salt diet (HSD) on the progression of high-fat diet (HFD)-induced metabolic dysfunction-associated steatohepatitis (MASH)-related liver fibrosis, as well as the underlying molecular mechanisms.

Methods

C57BL/6J mice were used to establish the following models: normal diet (Chow), HSD diet (Chow+8%salt), MASH diet (MASH), and MASH diet combined with HSD (MASH+8%salt). At the experience endpoint, the liver tissues were collected and subjected to HE staining, Sirius Red staining, immunohistochemistry (IHC) assay, and Oil Red O staining for histological assessment of steatosis, lipid deposition, and fibrosis. The levels of liver function indicators and serum lipids were measured and statistically analyzed, and the differences in liver weight, body weight, and their ratios were compared across the groups. RT-qPCR and Western blotting were applied to detect the mRNA and protein levels of hepatic fibrosis and inflammatory markers. Liver tissue samples were subjected to transcriptome sequencing, followed by bioinformatics analysis. Potential signaling pathways were validated through Western blotting to confirm the underlying mechanisms.

Results

Oil Red O and HE staining confirmed the successful establishment of the mouse models of MASH, MASH+8%salt, and Chow+8%salt. Serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), total cholesterol (Tch), and triglyceride (TG) showed no significant differences between the Chow+8%salt and Chow groups (P>0.05). In contrast, the MASH+8%salt group exhibited significantly higher AST and ALT levels than the MASH group (P<0.01), indicating that HSD exacerbates liver injury in the context of MASH. Sirius Red and α-SMA IHC staining revealed that HSD aggravated MASH-related liver fibrosis (P<0.01). Similarly, the mRNA levels of fibrosis activation-related genes (Col1a1, α-SMA, Timp1, Pdgfrβ) were more significantly up-regulated in the MASH+8%salt group (P<0.01). Protein expression levels of α-SMA and Fibronectin were also markedly elevated. Furthermore, the mRNA levels of inflammation-related genes (TNF-α, IL-6, IL-1β, TGF-β1) were obviously up-regulated in the MASH+8%salt group (P<0.05), suggesting that HSD promotes hepatitis and liver fibrosis progression in MASH. Transcriptome sequencing indicated significant activation of the PI3K/AKT/mTOR signaling pathway and up-regulation of the TGF-β pathway. Heatmap analysis demonstrated marked up-regulation of fibrosis- and inflammation-related genes. Western blotting confirmed significant activation of the PI3K/AKT/mTOR signaling pathway in the MASH+8%salt group (P<0.01).

Conclusion

High-salt diet promotes the progression of hepatitis and liver fibrosis in metabolic dysfunction associated steatohepatitis by activating the PI3K/AKT/mTOR signaling pathway.

, authors=Yin TANG, Jie ZHANG, Cui MAO, Tao XIONG, Chuanming XIE, Leida ZHANG, authorsList=Yin TANG, Jie ZHANG, Cui MAO, Tao XIONG, Chuanming XIE, Leida ZHANG, authorCompany=null, correspAuthors=Chuanming XIE, Leida ZHANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=© 2025 Journal of Army Medical University, copyrightOwner=Editorial Office of Journal of Army Medical University, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322954121669652970, articleId=1322954118091911646, tenantId=1146029695717560320, journalId=1319373162502258839, language=CN, title=高盐饮食通过PI3K/AKT/mTOR通路激活促进代谢功能障碍相关脂肪性肝炎纤维化进展, columnId=1320434418343329969, journalTitle=陆军军医大学学报, columnName=论著·基础医学, runingTitle=null, highlight=null, articleAbstract=
目的

探究小鼠高脂饮食模型建立的代谢功能障碍相关脂肪性肝炎（metabolic dysfunction-associated steatohepatitis，MASH）在联合高盐饮食背景下对MASH相关肝纤维化进展的影响及潜在的分子机制。

方法

采用C57BL/6J小鼠建立正常饮食小鼠模型、单纯高盐饮食小鼠模型、MASH小鼠模型和MASH联合高盐饮食模型，到达实验终点后取材分别对小鼠肝组织进行苏木素-伊红染色（hematoxylin-eosin staining，H-E）、天狼星红染色（Sirius staining）、免疫组织化学染色（immunohistochemistry，IHC）、油红O染色（Oil Red O）来对小鼠肝脏进行组织学层面评估其脂肪变性程度、脂质沉积及纤维化程度，另外统计分析小鼠肝功和血脂，比较小鼠肝重、体重及其比值变化，对小鼠肝脏组织纤维化标志物及其炎症标志物通过RT-qPCR和Western blot方法进行评估，将肝组织样品送转录组测序后进行生物信息学分析和通过Western blot方法对潜在信号通路进行验证以确认其可能的机制。

结果

通过油红O染色及H&E染色观察可以发现成功建立起代谢功能障碍相关脂肪性肝炎小鼠模型及其联合高盐饮食小鼠模型以及单纯高盐饮食小鼠模型，通过检测血清谷草转氨酶（aspartate transaminase，AST）、谷丙转氨酶（alanine aminotransferase，ALT）、总胆固醇（total cholesterol ，Tch）、甘油三酯（triglyceride，TG）水平可以发现单纯高盐饮食组小鼠在组织学层面与普通饮食组对比无显著差异（P>0.05），而MASH联合高盐饮食组较MASH饮食组AST、ALT水平升高更为显著（P<0.01），表明MASH背景下的高盐饮食可以加重肝损伤；另外通过天狼星红染色、α-SMA免疫组织化学染色发现MASH联合高盐饮食可以加剧MASH相关的肝纤维化（P<0.01），同样MASH联合高盐饮食组在反应纤维化激活相关基因Col1a1、α-SMA、Timp1、Pdgfrβ mRNA水平上表达升高更为显著（P<0.01），MASH联合高盐饮食组α-SMA和Fibronectin蛋白表达水平同样上调更为显著，除此之外反应炎症激活相关基因TNF-α、IL-6、IL-1β、TGF-β1在MASH联合高盐饮食组中表达水平明显上调（P<0.05），表明MASH联合高盐饮食促进了肝炎及肝纤维化发展；转录组测序分析显示PI3K/AKT/mTOR信号通路激活和TGF-β信号上调更为显著，热图显示纤维化和炎症相关基因显著上调；对富集信号通路相关分子进行Western blot实验验证显示MASH联合高盐饮食组的PI3K/AKT/mTOR信号通路显著激活（P<0.01）。

结论

高盐饮食通过PI3K/AKT/mTOR通路激活促进代谢功能障碍相关脂肪性肝炎纤维化进展。

, authors=唐银, 张捷, 毛毳, 熊涛, 谢传明, 张雷达, authorsList=唐银, 张捷, 毛毳, 熊涛, 谢传明, 张雷达, authorCompany=null, correspAuthors=谢传明, 张雷达, authorNote=null, correspAuthorsNote=
张雷达；E-mail：
谢传明，E-mail：
ZHANG Leida；E-mail：
XIE Chuanming，E-mail：
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=3PldPmJEdYABrGJ8CdAeTw==, magXml=e0iso0LU3rrPoRB+nRyUHg==, pdfUrl=null, pdf=PwvAVvDaRTWa6fbel+SdJQ==, pdfFileSize=1745557, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=A3VQuvYC7rJn+qxwmLK4YQ==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=A5LK/iNpphFlWA0B7EDTEg==, mapNumber=null, fund=null)}, authors=[Author(id=1322954122160386543, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954122261049841, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122160386543, language=EN, stringName=Yin TANG, firstName=Yin, middleName=null, lastName=TANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954122344935922, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122160386543, language=CN, stringName=唐银, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])]), Author(id=1322954122428822004, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954122567234038, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122428822004, language=EN, stringName=Jie ZHANG, firstName=Jie, middleName=null, lastName=ZHANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954122642731511, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122428822004, language=CN, stringName=张捷, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])]), Author(id=1322954122718228985, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954122823086587, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122718228985, language=EN, stringName=Cui MAO, firstName=Cui, middleName=null, lastName=MAO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954122919555580, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122718228985, language=CN, stringName=毛毳, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])]), Author(id=1322954123011830270, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=3, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954123087327744, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123011830270, language=EN, stringName=Tao XIONG, firstName=Tao, middleName=null, lastName=XIONG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954123229934081, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123011830270, language=CN, stringName=熊涛, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])]), Author(id=1322954123355763203, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=4, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=chuanming506@126.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1322954123582255621, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123355763203, language=EN, stringName=Chuanming XIE, firstName=Chuanming, middleName=null, lastName=XIE, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954123695501830, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123355763203, language=CN, stringName=谢传明, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])]), Author(id=1322954123959742985, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=5, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=zld666@aliyun.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1322954124052017675, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123959742985, language=EN, stringName=Leida ZHANG, firstName=Leida, middleName=null, lastName=ZHANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954125712962060, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123959742985, language=CN, stringName=张雷达, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])])], keywords=[Keyword(id=1322954125847179789, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, orderNo=1, keyword=metabolic dysfunction-associated steatohepatitis), Keyword(id=1322954125905900046, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, orderNo=2, keyword=high-salt diet), Keyword(id=1322954125964620303, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, orderNo=3, keyword=hepatitis), Keyword(id=1322954126048506384, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, orderNo=4, keyword=liver fibrosis), Keyword(id=1322954126132392465, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, orderNo=5, keyword=PI3K/AKT/mTOR signaling pathway), Keyword(id=1322954126249832978, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, orderNo=1, keyword=代谢功能障碍相关脂肪性肝炎), Keyword(id=1322954128195990035, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, orderNo=2, keyword=高盐饮食), Keyword(id=1322954128292459028, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, orderNo=3, keyword=肝炎), Keyword(id=1322954128405705237, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, orderNo=4, keyword=肝纤维化), Keyword(id=1322954130142147094, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, orderNo=5, keyword=PI3K/AKT/mTOR信号通路)], refs=[Reference(id=1322954131601764901, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.3350/cmh.2024.0478, pmid=null, pmcid=null, year=2025, volume=31, issue=1, pageStart=147, pageEnd=165, url=null, language=null, rfNumber=1, rfOrder=0, authorNames=HU S, WANG Z X, ZHU K, journalName=Clin Mol Hepatol, refType=null, unstructuredReference=HU S，WANG Z X，ZHU K，et al. USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination［J］. Clin Mol Hepatol，2025，31（1）：147-165., articleTitle=USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination, refAbstract=null), Reference(id=1322954131677262374, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1056/NEJMoa2105675, pmid=null, pmcid=null, year=2021, volume=385, issue=12, pageStart=1067, pageEnd=1077, url=null, language=null, rfNumber=2, rfOrder=1, authorNames=NEAL B, WU Y F, FENG X X, journalName=N Engl J Med, refType=null, unstructuredReference=NEAL B，WU Y F，FENG X X，et al. Effect of salt substitution on cardiovascular events and death［J］. N Engl J Med，2021，385（12）：1067-1077., articleTitle=Effect of salt substitution on cardiovascular events and death, refAbstract=null), Reference(id=1322954131748565543, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1186/s12931-024-02916-w, pmid=null, pmcid=null, year=2024, volume=25, issue=1, pageStart=288, pageEnd=null, url=null, language=null, rfNumber=3, rfOrder=2, authorNames=JIANG Q, YANG Q F, ZHANG C T, journalName=Respir Res, refType=null, unstructuredReference=JIANG Q，YANG Q F，ZHANG C T，et al. Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats［J］. Respir Res，2024，25（1）：288., articleTitle=Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats, refAbstract=null), Reference(id=1322954131836645928, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1111/jch.13551, pmid=null, pmcid=null, year=2019, volume=21, issue=6, pageStart=700, pageEnd=709, url=null, language=null, rfNumber=4, rfOrder=3, authorNames=CAMPBELL N R C, HE F J, TAN M, journalName=J Clin Hypertens （Greenwich）, refType=null, unstructuredReference=CAMPBELL N R C，HE F J，TAN M，et al. The International Consortium for Quality Research on Dietary Sodium/Salt （TRUE） position statement on the use of 24-hour，spot，and short duration （24 hours） timed urine collections to assess dietary sodium intake［J］. J Clin Hypertens （Greenwich），2019，21（6）：700-709., articleTitle=The International Consortium for Quality Research on Dietary Sodium/Salt （TRUE） position statement on the use of 24-hour，spot，and short duration （24 hours） timed urine collections to assess dietary sodium intake, refAbstract=null), Reference(id=1322954131912143401, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1111/liv.13750, pmid=null, pmcid=null, year=2018, volume=38, issue=7, pageStart=1148, pageEnd=1159, url=null, language=null, rfNumber=5, rfOrder=4, authorNames=HABERL J, ZOLLNER G, FICKERT P, journalName=Liver Int, refType=null, unstructuredReference=HABERL J，ZOLLNER G，FICKERT P，et al. To salt or not to salt？ -That is the question in cirrhosis［J］. Liver Int，2018，38（7）：1148-1159., articleTitle=To salt or not to salt？ -That is the question in cirrhosis, refAbstract=null), Reference(id=1322954131975057962, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.4254/wjh.v15.i10.1084, pmid=null, pmcid=null, year=2023, volume=15, issue=10, pageStart=1084, pageEnd=1090, url=null, language=null, rfNumber=6, rfOrder=5, authorNames=KUMAR R, MARRAPU S, journalName=World J Hepatol, refType=null, unstructuredReference=KUMAR R，MARRAPU S. Dietary salt in liver cirrhosis：With a pinch of salt！［J］. World J Hepatol，2023，15（10）：1084-1090., articleTitle=Dietary salt in liver cirrhosis：With a pinch of salt！, refAbstract=null), Reference(id=1322954132058944043, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1136/bmjopen-2013-003733, pmid=null, pmcid=null, year=2013, volume=3, issue=12, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=7, rfOrder=6, authorNames=POWLES J, FAHIMI S, MICHA R, journalName=BMJ Open, refType=null, unstructuredReference=POWLES J，FAHIMI S，MICHA R，et al. Global，regional and national sodium intakes in 1990 and 2010：a systematic analysis of 24 h urinary sodium excretion and dietary surveys worldwide［J］. BMJ Open，2013，3（12）：e003733., articleTitle=Global，regional and national sodium intakes in 1990 and 2010：a systematic analysis of 24 h urinary sodium excretion and dietary surveys worldwide, refAbstract=null), Reference(id=1322954132147024428, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1136/gutjnl-2023-331447, pmid=null, pmcid=null, year=2024, volume=73, issue=11, pageStart=1854, pageEnd=1869, url=null, language=null, rfNumber=8, rfOrder=7, authorNames=BABUTA M, MOREL C, DE CARVALHO RIBEIRO M, journalName=Gut, refType=null, unstructuredReference=BABUTA M，MOREL C，DE CARVALHO RIBEIRO M，et al. Neutrophil extracellular traps activate hepatic stellate cells and monocytes via NLRP3 sensing in alcohol-induced acceleration of MASH fibrosis［J］. Gut，2024，73（11）：1854-1869., articleTitle=Neutrophil extracellular traps activate hepatic stellate cells and monocytes via NLRP3 sensing in alcohol-induced acceleration of MASH fibrosis, refAbstract=null), Reference(id=1322954135661851181, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.3390/cells13110960, pmid=null, pmcid=null, year=2024, volume=13, issue=11, pageStart=960, pageEnd=null, url=null, language=null, rfNumber=9, rfOrder=8, authorNames=BABUTA M, NAGESH P T, DATTA A A, journalName=Cells, refType=null, unstructuredReference=BABUTA M，NAGESH P T，DATTA A A，et al. Combined insults of a MASH diet and alcohol binges activate intercellular communication and neutrophil recruitment via the NLRP3-IL-1β axis in the liver［J］. Cells，2024，13（11）：960., articleTitle=Combined insults of a MASH diet and alcohol binges activate intercellular communication and neutrophil recruitment via the NLRP3-IL-1β axis in the liver, refAbstract=null), Reference(id=1322954135758320174, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1161/CIRCULATIONAHA. 121.055600, pmid=null, pmcid=null, year=2022, volume=145, issue=5, pageStart=375, pageEnd=391, url=null, language=null, rfNumber=10, rfOrder=9, authorNames=GAO P, YOU M, LI L, journalName=Circulation, refType=null, unstructuredReference=GAO P，YOU M，LI L，et al. Salt-induced hepatic inflammatory memory contributes to cardiovascular damage through epigenetic modulation of SIRT3［J］. Circulation，2022，145（5）：375-391., articleTitle=Salt-induced hepatic inflammatory memory contributes to cardiovascular damage through epigenetic modulation of SIRT3, refAbstract=null), Reference(id=1322954135846400559, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1186/s12876-021-01912-4, pmid=null, pmcid=null, year=2021, volume=21, issue=1, pageStart=335, pageEnd=null, url=null, language=null, rfNumber=11, rfOrder=10, authorNames=LI Y P, LYU Y F, HUANG J, journalName=BMC Gastroenterol, refType=null, unstructuredReference=LI Y P，LYU Y F，HUANG J，et al. Transcriptome sequencing reveals high-salt diet-induced abnormal liver metabolic pathways in mice［J］. BMC Gastroenterol，2021，21（1）：335., articleTitle=Transcriptome sequencing reveals high-salt diet-induced abnormal liver metabolic pathways in mice, refAbstract=null), Reference(id=1322954135951258160, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1371/journal.pone.0143222, pmid=null, pmcid=null, year=2015, volume=10, issue=11, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=12, rfOrder=11, authorNames=HUH J H, LEE K J, LIM J S, journalName=PLoS One, refType=null, unstructuredReference=HUH J H，LEE K J，LIM J S，et al. High dietary sodium intake assessed by estimated 24-h urinary sodium excretion is associated with NAFLD and hepatic fibrosis［J］. PLoS One，2015，10（11）：e0143222., articleTitle=High dietary sodium intake assessed by estimated 24-h urinary sodium excretion is associated with NAFLD and hepatic fibrosis, refAbstract=null), Reference(id=1322954136056115761, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1021/acs.jafc.5b05897, pmid=null, pmcid=null, year=2016, volume=64, issue=7, pageStart=1610, pageEnd=1617, url=null, language=null, rfNumber=13, rfOrder=12, authorNames=WANG G, YEUNG C K, WONG W Y, journalName=J Agric Food Chem, refType=null, unstructuredReference=WANG G，YEUNG C K，WONG W Y，et al. Liver fibrosis can be induced by high salt intake through excess reactive oxygen species （ROS） production［J］. J Agric Food Chem，2016，64（7）：1610-1617., articleTitle=Liver fibrosis can be induced by high salt intake through excess reactive oxygen species （ROS） production, refAbstract=null), Reference(id=1322954136156779058, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1111/cpr.13435, pmid=null, pmcid=null, year=2023, volume=56, issue=6, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=14, rfOrder=13, authorNames=TANG Q Y, MARKBY G R, MACNAIR A J, journalName=Cell Prolif, refType=null, unstructuredReference=TANG Q Y，MARKBY G R，MACNAIR A J，et al. TGF-β-induced PI3K/AKT/mTOR pathway controls myofibroblast differentiation and secretory phenotype of valvular interstitial cells through the modulation of cellular senescence in a naturally occurring in vitro canine model of myxomatous mitral valve disease［J］. Cell Prolif，2023，56（6）：e13435., articleTitle=TGF-β-induced PI3K/AKT/mTOR pathway controls myofibroblast differentiation and secretory phenotype of valvular interstitial cells through the modulation of cellular senescence in a naturally occurring in vitro canine model of myxomatous mitral valve disease, refAbstract=null), Reference(id=1322954136240665139, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1101/cshperspect.a022137, pmid=null, pmcid=null, year=2017, volume=9, issue=1, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=15, rfOrder=14, authorNames=LUO K X, journalName=Cold Spring Harb Perspect Biol, refType=null, unstructuredReference=LUO K X. Signaling cross talk between TGF-β/smad and other signaling pathways［J］. Cold Spring Harb Perspect Biol，2017，9（1）：a022137., articleTitle=Signaling cross talk between TGF-β/smad and other signaling pathways, refAbstract=null), Reference(id=1322954136374882868, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.2147/DDDT.S194787, pmid=null, pmcid=null, year=2019, volume=13, issue=null, pageStart=1889, pageEnd=1900, url=null, language=null, rfNumber=16, rfOrder=15, authorNames=WANG R, SONG F X, LI S N, journalName=Drug Des Devel Ther, refType=null, unstructuredReference=WANG R，SONG F X，LI S N，et al. Salvianolic acid A attenuates CCl（4）-induced liver fibrosis by regulating the PI3K/AKT/mTOR，Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways［J］. Drug Des Devel Ther，2019，13：1889-1900., articleTitle=Salvianolic acid A attenuates CCl（4）-induced liver fibrosis by regulating the PI3K/AKT/mTOR，Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways, refAbstract=null), Reference(id=1322954136475546165, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1172/JCI166149, pmid=null, pmcid=null, year=2024, volume=134, issue=5, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=17, rfOrder=16, authorNames=XU S W, WU X M, WANG S C, journalName=J Clin Invest, refType=null, unstructuredReference=XU S W，WU X M，WANG S C，et al. TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase［J］. J Clin Invest，2024，134（5）：e166149., articleTitle=TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase, refAbstract=null), Reference(id=1322954136580403766, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.3389/fpls.2024.1351008, pmid=null, pmcid=null, year=2024, volume=15, issue=null, pageStart=1351008, pageEnd=null, url=null, language=null, rfNumber=18, rfOrder=17, authorNames=ZHAO K N, LAN Y B, SHI Y, journalName=Front Plant Sci, refType=null, unstructuredReference=ZHAO K N，LAN Y B，SHI Y，et al. Metabolite and transcriptome analyses reveal the effects of salinity stress on the biosynthesis of proanthocyanidins and anthocyanins in grape suspension cells［J］. Front Plant Sci，2024，15：1351008., articleTitle=Metabolite and transcriptome analyses reveal the effects of salinity stress on the biosynthesis of proanthocyanidins and anthocyanins in grape suspension cells, refAbstract=null), Reference(id=1322954136647512631, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1016/j.jhepr.2025.101454, pmid=null, pmcid=null, year=2025, volume=7, issue=8, pageStart=101454, pageEnd=null, url=null, language=null, rfNumber=19, rfOrder=18, authorNames=NAVARRO-CORCUERA A, ZHU Y W, MA F L, journalName=JHEP Rep, refType=null, unstructuredReference=NAVARRO-CORCUERA A，ZHU Y W，MA F L，et al. Resolvin D1-mediated cellular crosstalk protects against MASH［J］. JHEP Rep，2025，7（8）：101454., articleTitle=Resolvin D1-mediated cellular crosstalk protects against MASH, refAbstract=null), Reference(id=1322954136714621496, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.16016/j.2097-0927.202412024, pmid=null, pmcid=null, year=2025, volume=47, issue=9, pageStart=969, pageEnd=979, url=null, language=null, rfNumber=20, rfOrder=19, authorNames=秦嘉怡, 周学谦, 孟祥勇, journalName=陆军军医大学学报, refType=null, unstructuredReference=秦嘉怡，周学谦，孟祥勇，等. 瘦型代谢功能障碍相关脂肪性肝病风险预测模型的构建与验证［J］. 陆军军医大学学报，2025，47（9）：969-979., articleTitle=瘦型代谢功能障碍相关脂肪性肝病风险预测模型的构建与验证, refAbstract=null), Reference(id=1322954136865616441, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.16016/j.2097-0927.202412024, pmid=null, pmcid=null, year=2025, volume=47, issue=9, pageStart=969, pageEnd=979, url=null, language=null, rfNumber=20, rfOrder=20, authorNames=QIN J Y, ZHOU X Q, MENG X Y, journalName=J Army Med Univ, refType=null, unstructuredReference=QIN J Y，ZHOU X Q，MENG X Y，et al. Construction and validation of a risk prediction model for lean metabolic dysfunction-associated steatotic liver disease［J］. J Army Med Univ，2025，47（9）：969-979., articleTitle=Construction and validation of a risk prediction model for lean metabolic dysfunction-associated steatotic liver disease, refAbstract=null), Reference(id=1322954136941113914, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1001/jama.1983.03340030048029, pmid=null, pmcid=null, year=1983, volume=250, issue=3, pageStart=388, pageEnd=null, url=null, language=null, rfNumber=21, rfOrder=21, authorNames=SCRIBNER B H, journalName=JAMA, refType=null, unstructuredReference=SCRIBNER B H. Salt and hypertension［J］. JAMA，1983，250（3）：388., articleTitle=Salt and hypertension, refAbstract=null), Reference(id=1322954137045971515, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=null, pmid=null, pmcid=null, year=1985, volume=142, issue=9, pageStart=497, pageEnd=498, url=null, language=null, rfNumber=22, rfOrder=22, authorNames=DWYER T, journalName=Med J Aust, refType=null, unstructuredReference=DWYER T. Salt and hypertension ［J］. Med J Aust，1985，142（9）：497-498., articleTitle=Salt and hypertension, refAbstract=null), Reference(id=1322954137138246204, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1016/S0140-6736（80）91631-1, pmid=null, pmcid=null, year=1980, volume=315, issue=8179, pageStart=1177, pageEnd=1179, url=null, language=null, rfNumber=23, rfOrder=23, authorNames=SWALES J D, journalName=Lancet, refType=null, unstructuredReference=SWALES J D. Dietary salt and hypertension［J］. Lancet，1980，315（8179）：1177-1179., articleTitle=Dietary salt and hypertension, refAbstract=null), Reference(id=1322954137226326589, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1016/j.jnutbio.2024.109808, pmid=null, pmcid=null, year=2025, volume=136, issue=null, pageStart=109808, pageEnd=null, url=null, language=null, rfNumber=24, rfOrder=24, authorNames=LIU R, ZHANG Y, LIU M, journalName=J Nutr Biochem, refType=null, unstructuredReference=LIU R，ZHANG Y，LIU M，et al. Natural molecule isoliquiritigenin mitigates MASH and liver fibrosis in mice by promoting autophagy through the PI3K/Akt signaling pathway［J］. J Nutr Biochem，2025，136：109808., articleTitle=Natural molecule isoliquiritigenin mitigates MASH and liver fibrosis in mice by promoting autophagy through the PI3K/Akt signaling pathway, refAbstract=null), Reference(id=1322954137335378494, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1111/iep.12519, pmid=null, pmcid=null, year=2024, volume=105, issue=6, pageStart=219, pageEnd=234, url=null, language=null, rfNumber=25, rfOrder=25, authorNames=FARRASH W F, IDRIS S, ELZUBIER M E, journalName=Int J Exp Pathol, refType=null, unstructuredReference=FARRASH W F，IDRIS S，ELZUBIER M E，et al. Enhanced hepatoprotective effects of empagliflozin and vitamin D dual therapy against metabolic dysfunction-associated steatohepatitis in mice by boosted modulation of metabolic，oxidative stress，and inflammatory pathways［J］. Int J Exp Pathol，2024，105（6）：219-234., articleTitle=Enhanced hepatoprotective effects of empagliflozin and vitamin D dual therapy against metabolic dysfunction-associated steatohepatitis in mice by boosted modulation of metabolic，oxidative stress，and inflammatory pathways, refAbstract=null), Reference(id=1322954137402487359, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1016/j.ejphar.2024.177069, pmid=null, pmcid=null, year=2024, volume=984, issue=null, pageStart=177069, pageEnd=null, url=null, language=null, rfNumber=26, rfOrder=26, authorNames=EZZ-ELDIN Y M, EL-DIN EWEES M G, KHALAF M M, journalName=Eur J Pharmacol, refType=null, unstructuredReference=EZZ-ELDIN Y M，EL-DIN EWEES M G，KHALAF M M，et al. Modulation of SIRT6 related signaling pathways of p-AKT/mTOR and NRF2/HO-1 by memantine contributes to curbing the progression of tamoxifen/HFD-induced MASH in rats［J］. Eur J Pharmacol，2024，984：177069., articleTitle=Modulation of SIRT6 related signaling pathways of p-AKT/mTOR and NRF2/HO-1 by memantine contributes to curbing the progression of tamoxifen/HFD-induced MASH in rats, refAbstract=null), Reference(id=1322954139071820352, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1186/s12951-023-01788-4, pmid=null, pmcid=null, year=2023, volume=21, issue=1, pageStart=29, pageEnd=null, url=null, language=null, rfNumber=27, rfOrder=27, authorNames=ZHANG Z L, SHANG J, YANG Q Y, journalName=J Nanobiotechnology, refType=null, unstructuredReference=ZHANG Z L，SHANG J，YANG Q Y，et al. Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism［J］. J Nanobiotechnology，2023，21（1）：29., articleTitle=Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism, refAbstract=null), Reference(id=1322954139180872257, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.3389/fmed.2025.1628260, pmid=null, pmcid=null, year=2025, volume=12, issue=null, pageStart=1628260, pageEnd=null, url=null, language=null, rfNumber=28, rfOrder=28, authorNames=LI X N, LIU X, SHI X R, journalName=Front Med, refType=null, unstructuredReference=LI X N，LIU X，SHI X R，et al. REDD1 attenuates cholestatic liver fibrosis and suppresses PI3K/AKT/mTOR pathway［J］. Front Med，2025，12：1628260., articleTitle=REDD1 attenuates cholestatic liver fibrosis and suppresses PI3K/AKT/mTOR pathway, refAbstract=null), Reference(id=1322954139256369730, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1016/j.metabol.2020.154186, pmid=null, pmcid=null, year=2020, volume=105, issue=null, pageStart=154186, pageEnd=null, url=null, language=null, rfNumber=29, rfOrder=29, authorNames=GEORGILA K, GOUNIS M, HAVAKI S, journalName=Metabolism, refType=null, unstructuredReference=GEORGILA K，GOUNIS M，HAVAKI S，et al. mTORC1-dependent protein synthesis and autophagy uncouple in the regulation of Apolipoprotein A-I expression［J］. Metabolism，2020，105：154186., articleTitle=mTORC1-dependent protein synthesis and autophagy uncouple in the regulation of Apolipoprotein A-I expression, refAbstract=null), Reference(id=1322954139327672899, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.3892/mmr.2010.365, pmid=null, pmcid=null, year=2010, volume=3, issue=6, pageStart=909, pageEnd=915, url=null, language=null, rfNumber=30, rfOrder=30, authorNames=WANG Y G, SHI M, FU H Y, journalName=Mol Med Rep, refType=null, unstructuredReference=WANG Y G，SHI M，FU H Y，et al. Mammalian target of the rapamycin pathway is involved in non-alcoholic fatty liver disease［J］. Mol Med Rep，2010，3（6）：909-915., articleTitle=Mammalian target of the rapamycin pathway is involved in non-alcoholic fatty liver disease, refAbstract=null), Reference(id=1322954139398976068, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1016/j.devcel.2022.02.024, pmid=null, pmcid=null, year=2022, volume=57, issue=6, pageStart=691, pageEnd=706, url=null, language=null, rfNumber=31, rfOrder=31, authorNames=SIMCOX J, LAMMING D W, journalName=Dev Cell, refType=null, unstructuredReference=SIMCOX J，LAMMING D W. The central moTOR of metabolism［J］. Dev Cell，2022，57（6）：691-706., articleTitle=The central moTOR of metabolism, refAbstract=null), Reference(id=1322954139453502021, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.3389/fendo.2018.00539, pmid=null, pmcid=null, year=2018, volume=9, issue=null, pageStart=539, pageEnd=null, url=null, language=null, rfNumber=32, rfOrder=32, authorNames=LEE Y S, PARK J S, LEE D H, journalName=Front Endocrinol, refType=null, unstructuredReference=LEE Y S，PARK J S，LEE D H，et al. The antidiabetic drug lobeglitazone protects mice from lipogenesis-induced liver injury via mechanistic target of rapamycin complex 1 inhibition［J］. Front Endocrinol，2018，9：539., articleTitle=The antidiabetic drug lobeglitazone protects mice from lipogenesis-induced liver injury via mechanistic target of rapamycin complex 1 inhibition, refAbstract=null), Reference(id=1322954139554165318, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.1007/s11011-024-01358-z, pmid=null, pmcid=null, year=2024, volume=39, issue=5, pageStart=803, pageEnd=819, url=null, language=null, rfNumber=33, rfOrder=33, authorNames=LIU S, YANG X, YUAN M H, journalName=Metab Brain Dis, refType=null, unstructuredReference=LIU S，YANG X，YUAN M H，et al. High salt diet induces cognitive impairment and is linked to the activation of IGF1R/mTOR/p70S6K signaling［J］. Metab Brain Dis，2024，39（5）：803-819., articleTitle=High salt diet induces cognitive impairment and is linked to the activation of IGF1R/mTOR/p70S6K signaling, refAbstract=null), Reference(id=1322954139625468487, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, doi=10.3390/ijms17040480, pmid=null, pmcid=null, year=2016, volume=17, issue=4, pageStart=480, pageEnd=null, url=null, language=null, rfNumber=34, rfOrder=34, authorNames=WANG D, WANG Y, LIU F Q, journalName=Int J Mol Sci, refType=null, unstructuredReference=WANG D，WANG Y，LIU F Q，et al. High salt diet affects renal sodium excretion and ERRα expression［J］. Int J Mol Sci，2016，17（4）：480., articleTitle=High salt diet affects renal sodium excretion and ERRα expression, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])], figs=[ArticleFig(id=1322954130309919255, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, label=Figure 1, caption=Schematic diagram of mouse modeling and comparative evaluation of body weight，liver weight，liver morphology，and liver function across groups, figureFileSmall=ehfWcdeWY75YcUJORADz1w==, figureFileBig=A3VQuvYC7rJn+qxwmLK4YQ==, tableContent=null), ArticleFig(id=1322954130406388248, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, label=图1, caption=小鼠建模示意图及体重、肝重、肝形态学，肝功能比较评估

A：Schematic detailing the process of animal modelling； B：Gross observation for mice of each group； C：Gross morphology of the isolated liver； D~I：Statistical analyses on body weight （D），ratio of liver to body weight （E），and serum levels of total cholesterol （Tch，F），triglyceride （TG，G），aspartate aminotransferase （AST，H） and alanine aminotransferase （ALT，I） across the groups of mice. a：P<0.05，b：P<0.01，c：P<0.001

, figureFileSmall=ehfWcdeWY75YcUJORADz1w==, figureFileBig=A3VQuvYC7rJn+qxwmLK4YQ==, tableContent=null), ArticleFig(id=1322954130586743321, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, label=Figure 2, caption=High-salt diet exacerbates hepatic inflammation and fibrosis in the context of MASH, figureFileSmall=9U1qOBjD+0NPutwVWGSbeA==, figureFileBig=1WFyXwy2s8C2MzWoHV35IQ==, tableContent=null), ArticleFig(id=1322954130687406618, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, label=图2, caption=高盐饮食加剧MASH背景下的肝炎及肝纤维化

A~D：Hepatic mRNA expression levels of fibrosis markers （α-SMA，Col1a1，Timp-1，Pdgfrβ） in the 4 groups as detected by RT-qPCR （n=6）； E：Representative images of HE staining，Sirius Red staining，and α-SMA immunohistochemical staining of liver sections from the 4 groups； F~I：Quantitative analysis of liver fibrosis score，steatosis score，Sirius Red-positive area percentage，and α-SMA-positive area percentage in the 4 groups （n=6）. a：P<0.05，b：P<0.01，c：P<0.001

, figureFileSmall=9U1qOBjD+0NPutwVWGSbeA==, figureFileBig=1WFyXwy2s8C2MzWoHV35IQ==, tableContent=null), ArticleFig(id=1322954130767098395, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, label=Figure 2（Continued）, caption=High-salt diet exacerbates hepatic inflammation and fibrosis in the context of MASH, figureFileSmall=4UgDWzKCu/RIyYewiS8+Pg==, figureFileBig=UZfHvz6A75+hd/EFPGfb8g==, tableContent=null), ArticleFig(id=1322954130892927516, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, label=续图2, caption=高盐饮食加剧MASH背景下的肝炎及肝纤维化

J：Representative images of Oil Red O staining of liver tissues from the 4 groups； K：Protein expression levels of Fibronectin and α-SMA in liver tissues from the 4 groups as detected by Western blotting （n=3）； L~O：Hepatic mRNA expression levels of inflammatory markers （IL-6，TNF-α，IL-1β，TGF-β1） in the 4 groups as detected by RT-qPCR （n=6）. a：P<0.05，b：P<0.01，c：P<0.001

, figureFileSmall=4UgDWzKCu/RIyYewiS8+Pg==, figureFileBig=UZfHvz6A75+hd/EFPGfb8g==, tableContent=null), ArticleFig(id=1322954130955842077, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, label=Figure 3, caption=Transcriptomic characteristics and signaling pathway enrichment in liver tissues of mice subjected to MASH with a high-salt diet, figureFileSmall=N0UkzvgR0gds08ALuew4sA==, figureFileBig=HY296VjnpyFwKOrRmrvT4A==, tableContent=null), ArticleFig(id=1322954131022950942, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, label=图3, caption=MASH联合高盐饮食小鼠肝组织转录组特征及信号通路富集

A：Volcano plot of transcriptome data showing differentially expressed genes in MASH with high-salt diet versus MASH diet alone； B，E：KEGG enrichment analysis reveals significant enrichment of the PI3K/AKT signaling pathway in the MASH with high-salt diet group； C：Heatmap demonstrating up-regulation of fibrosis and inflammation related genes in the MASH with high-salt diet group； D：KEGG enrichment analysis shows significant enrichment of the TGF-β signaling pathway in the MASH with high-salt diet group

, figureFileSmall=N0UkzvgR0gds08ALuew4sA==, figureFileBig=HY296VjnpyFwKOrRmrvT4A==, tableContent=null), ArticleFig(id=1322954131119419935, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, label=Figure 4, caption=Validation of signaling pathway molecule expression by Western blot analysis in mouse liver tissues, figureFileSmall=WE5t1vYVgpHlnjjWPF2vgA==, figureFileBig=H6F96fSHCecmcJhfeK/PMA==, tableContent=null), ArticleFig(id=1322954131190723104, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, label=图4, caption=小鼠肝脏组织蛋白质免疫印迹实验验证信号通路分子表达

A：Western blot analysis of p-mTOR，p-ERK，p-AKT，p-4EBP1，and p-70S6K protein expression levels in liver tissues from the 4 groups； B：Quantitative analysis and comparison of p-mTOR，p-ERK，p-AKT，p-4EBP1，and p-70S6K protein expression levels； C：Western blot analysis of LX-2 cells treated with NaCl （200 mmol/L），sodium palmitate （PA，500 μmol/L），and rapamycin （100 nmol/L） for 48 h. a：P<0.05，b：P<0.01，c：P<0.001

, figureFileSmall=WE5t1vYVgpHlnjjWPF2vgA==, figureFileBig=H6F96fSHCecmcJhfeK/PMA==, tableContent=null), ArticleFig(id=1322954131253637665, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, label=Table 1, caption=

Primer sequences for RT-qPCR

, figureFileSmall=null, figureFileBig=null, tableContent=
Gene nameForward primer（5′→3′）Reverse primer（5′→3′）
Mouse α-Sma
Mouse Col1a1
Mouse Pdgfrβ
Mouse Timp-1
Mouse Il-6
Mouse Il-1β
Mouse Tnf-α
Mouse Tgf-β1
Mouse Gapdh		CCGCCATGTATGTGGCTATT
TAAGGGTCCCCAATGGTGAGA
TCCCACATTCCTTGCCCTTC
CGAGACCACCTTATACCAGCG
GAGCCCACCAAGAACGATAG
GCTTCAGGCAGGCAGTATCA
CAAGATGCTGGGACAGTGAC
CTCCCGTGGCTTCTAGTGC
AGACGGCCGCATCTTCTT		CAGTTGTACGTCCAGAGGCATA
GGGTCCCTCGACTCCTACAT
GCACAGGGTCCACGTAGATG
GGCGTACCGGATATCTGCG
TCATTTCCACGATTTCCCAG
GACAGCACGAGGCTTTTTTG
AGGGAAGAATCTGGAAAGGT
GCCTTAGTTTGGACAGGATCTG
TTCACACCGACCTTCACCAT
), ArticleFig(id=1322954131362689570, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, label=表1, caption=

RT-qPCR实验使用引物序列

, figureFileSmall=null, figureFileBig=null, tableContent=
Gene nameForward primer（5′→3′）Reverse primer（5′→3′）
Mouse α-Sma
Mouse Col1a1
Mouse Pdgfrβ
Mouse Timp-1
Mouse Il-6
Mouse Il-1β
Mouse Tnf-α
Mouse Tgf-β1
Mouse Gapdh		CCGCCATGTATGTGGCTATT
TAAGGGTCCCCAATGGTGAGA
TCCCACATTCCTTGCCCTTC
CGAGACCACCTTATACCAGCG
GAGCCCACCAAGAACGATAG
GCTTCAGGCAGGCAGTATCA
CAAGATGCTGGGACAGTGAC
CTCCCGTGGCTTCTAGTGC
AGACGGCCGCATCTTCTT		CAGTTGTACGTCCAGAGGCATA
GGGTCCCTCGACTCCTACAT
GCACAGGGTCCACGTAGATG
GGCGTACCGGATATCTGCG
TCATTTCCACGATTTCCCAG
GACAGCACGAGGCTTTTTTG
AGGGAAGAATCTGGAAAGGT
GCCTTAGTTTGGACAGGATCTG
TTCACACCGACCTTCACCAT
), ArticleFig(id=1322954131429798435, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=EN, label=Table 2, caption=

Catalogue numbers and dilutions of primary antibodies for Western blotting

, figureFileSmall=null, figureFileBig=null, tableContent=
AntibodiesCatalogue No.Dilution
P-mTORCST，Cat. #：5536S1∶1 000
T-mTORCST，Cat. #：2983S1∶1 000
α-SMACST，Cat. #：489381∶1 000
p-AKTCST，Cat. #：4060S1∶1 000
T-AKTCST，Cat. #：4691S1∶1 000
p-S6KCST，Cat. #：2211S1∶1 000
p-4EBP1CST，Cat. #：2855S1∶1 000
T-4EBP1CST，Cat. #：9644S1∶1 000
FibronectinProteintech，Cat# 15613-1-AP1∶1 000
β-actinproteintech，Cat# 20536-1-AP1∶5 000
GAPDHproteintech，Cat# 10494-1-AP1∶5 000
), ArticleFig(id=1322954131501101604, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, language=CN, label=表2, caption=

WB实验一抗抗体货号、浓度

, figureFileSmall=null, figureFileBig=null, tableContent=
AntibodiesCatalogue No.Dilution
P-mTORCST，Cat. #：5536S1∶1 000
T-mTORCST，Cat. #：2983S1∶1 000
α-SMACST，Cat. #：489381∶1 000
p-AKTCST，Cat. #：4060S1∶1 000
T-AKTCST，Cat. #：4691S1∶1 000
p-S6KCST，Cat. #：2211S1∶1 000
p-4EBP1CST，Cat. #：2855S1∶1 000
T-4EBP1CST，Cat. #：9644S1∶1 000
FibronectinProteintech，Cat# 15613-1-AP1∶1 000
β-actinproteintech，Cat# 20536-1-AP1∶5 000
GAPDHproteintech，Cat# 10494-1-AP1∶5 000
)], attaches=null, journal=Journal(id=1319372634082869396, delFlag=0, nameCn=陆军军医大学学报, nameEn=Journal of Army Medical University, nameHistory1=null, nameHistory2=null, issn=2097-0927, eissn=null, cn=50-1223/R, coden=null, periodic=3, language=CN, oaType=null, ccby=null, superviseOffice=null, ownerOffice=null, pubOffice=null, editorOffice=null, officeType=null, aims=null, clcCode=null, officeProv=null, officeCity=null, officeAddr=null, officeZip=null, officeEmail=null, officePhone=null, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=zdiTazv9TbsMJqLaCJ/k7A==, journalPrice=null, startedYear=null, abbrevIsoEn=Journal of Army Medical University, journalRemark=null, publicationField=null, createdTime=1792492548725, updatedTime=1792745216517, createdBy=18614031015, updatedBy=13701087609, firstLetterCn=L, firstLetterEn=L, subjectCode=Medical and Pharmaceutical Sciences, subjectName=null, subjectCodeEn=Medical and Pharmaceutical Sciences, subjectNameEn=null, picCn=zdiTazv9TbsMJqLaCJ/k7A==, picEn=931BgeD2k9AIsc7QjHoQKg==, jcr=null, cjcr=null, exts=[JournalExt(id=1320432400862135101, language=CN, name=陆军军医大学学报, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1792745216813, updatedTime=1792745216813, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://ljjydx.portal.founderss.cn, submissionEditorUrl=https://journal.ids.fzyun.cn, submissionReviewUrl=https://ljjydx.portal.founderss.cn, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1320432400933438270, language=EN, name=Journal of Army Medical University, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1792745216830, updatedTime=1792745216830, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://ljjydx.portal.founderss.cn, submissionEditorUrl=https://journal.ids.fzyun.cn, submissionReviewUrl=https://ljjydx.portal.founderss.cn, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1319373162502258839, websiteList=[Website(id=1319376331821925278, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1319373162502258839, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN, language=CN, createTime=1792493430333, createBy=18614031015, updateTime=1792493552921, updateBy=18614031015, name=陆军军医大学学报-中文, tplId=1146099689490845704, title=陆军军医大学学报, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1319376971570729589, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=articleTextType, value=kx, createTime=1792493582861, updateTime=1792493582861, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971549758066, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=banner, value=null, createTime=1792493582856, updateTime=1792493582856, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971591701112, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=grayFlag, value=0, createTime=1792493582866, updateTime=1792493582866, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971541369457, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=logo, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/file/pic?fileId=Mmvh7crXM7dcUwf9n9+ehg==, createTime=1792493582854, updateTime=1792493582854, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971608478330, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=minRunFlag, value=0, createTime=1792493582870, updateTime=1792493582870, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971562340980, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/file/pic, createTime=1792493582859, updateTime=1792493582859, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971600089721, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=silenceFlag, value=0, createTime=1792493582868, updateTime=1792493582868, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971558146675, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1792493582858, updateTime=1792493582858, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971574923894, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=themeColor, value=null, createTime=1792493582862, updateTime=1792493582862, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971583312503, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=themeStyle, value=null, createTime=1792493582864, updateTime=1792493582864, creator=18614031015, updator=18614031015)]), Website(id=1319376331905811365, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1319373162502258839, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN, language=EN, createTime=1792493430353, createBy=18614031015, updateTime=1792493548158, updateBy=18614031015, name=陆军军医大学学报-英文, tplId=1146101810881728533, title=Journal of Army Medical University, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1319376935873008230, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=articleTextType, value=kx, createTime=1792493574350, updateTime=1792493574350, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935843648099, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=banner, value=null, createTime=1792493574343, updateTime=1792493574343, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935902368361, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=grayFlag, value=0, createTime=1792493574357, updateTime=1792493574357, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935835259490, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=logo, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/file/pic?fileId=Mmvh7crXM7dcUwf9n9+ehg==, createTime=1792493574341, updateTime=1792493574341, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935914951275, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=minRunFlag, value=0, createTime=1792493574360, updateTime=1792493574360, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935864619621, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/file/pic, createTime=1792493574348, updateTime=1792493574348, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935906562666, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=silenceFlag, value=0, createTime=1792493574358, updateTime=1792493574358, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935856231012, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1792493574346, updateTime=1792493574346, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935881396839, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=themeColor, value=null, createTime=1792493574352, updateTime=1792493574352, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935889785448, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=themeStyle, value=null, createTime=1792493574354, updateTime=1792493574354, creator=18614031015, updator=18614031015)])], journalTitle=陆军军医大学学报, weixinUrl=null, journalUrl=https://aammt.tmmu.edu.cn/, iacademicId=null, status=1, seqNo=null, journalTitleEn=Journal of Army Medical University, journalPhotoCn=zdiTazv9TbsMJqLaCJ/k7A==, journalPhotoEn=931BgeD2k9AIsc7QjHoQKg==, journalFirstLetter=L, journalRecommend=null, journalNew=null, journalCollection=null, jcrJf=null, cjcrJf=null, jcrJfStr=null, cjcrJfStr=null, submissionFirstDecision=null, sciSubjectClassification=null, casSubjectClassification=null, citeScore=null, totalCitationFrequency=null, icpCode=null, psCode=null, advertisingLicenseCode=null, copyrightInformation=null, country=null, option=, provinceCode=null, provinceName=null, collectFlag=false, interPubPlatform=, interPubPlatformUrl=null), detailUrlCn=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/10.16016/j.2097-0927.202511049, detailUrlEn=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/10.16016/j.2097-0927.202511049, pdfUrlCn=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/PDF/10.16016/j.2097-0927.202511049, pdfUrlEn=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/PDF/10.16016/j.2097-0927.202511049, aliStartDate=0, aliEndDate=0, collectionFlag=false, citedCount=null, citedUrl=null, previewStatus=0, delFlag=0, hasFullText=1, orderTime=1767024000000, fullTextJson=null, articleText=null, reference=null)
收藏切换
高盐饮食通过PI3K/AKT/mTOR通路激活促进代谢功能障碍相关脂肪性肝炎纤维化进展
收藏切换
PDF下载
唐银 , 张捷 , 毛毳 , 熊涛 , 谢传明 , 张雷达
陆军军医大学学报 | 论著·基础医学 2025,47(24): 3009-3021
收起
收藏切换
陆军军医大学学报 |论著·基础医学 2025 , 47 (24) : 3009 -3021
高盐饮食通过PI3K/AKT/mTOR通路激活促进代谢功能障碍相关脂肪性肝炎纤维化进展
全屏
[Author(id=1322954122160386543, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954122261049841, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122160386543, language=EN, stringName=Yin TANG, firstName=Yin, middleName=null, lastName=TANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954122344935922, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122160386543, language=CN, stringName=唐银, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])]), Author(id=1322954122428822004, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954122567234038, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122428822004, language=EN, stringName=Jie ZHANG, firstName=Jie, middleName=null, lastName=ZHANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954122642731511, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122428822004, language=CN, stringName=张捷, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])]), Author(id=1322954122718228985, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954122823086587, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122718228985, language=EN, stringName=Cui MAO, firstName=Cui, middleName=null, lastName=MAO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954122919555580, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954122718228985, language=CN, stringName=毛毳, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])]), Author(id=1322954123011830270, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=3, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954123087327744, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123011830270, language=EN, stringName=Tao XIONG, firstName=Tao, middleName=null, lastName=XIONG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954123229934081, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123011830270, language=CN, stringName=熊涛, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])]), Author(id=1322954123355763203, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=4, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=chuanming506@126.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1322954123582255621, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123355763203, language=EN, stringName=Chuanming XIE, firstName=Chuanming, middleName=null, lastName=XIE, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954123695501830, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123355763203, language=CN, stringName=谢传明, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])]), Author(id=1322954123959742985, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, orderNo=5, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=zld666@aliyun.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1322954124052017675, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123959742985, language=EN, stringName=Leida ZHANG, firstName=Leida, middleName=null, lastName=ZHANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954125712962060, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, authorId=1322954123959742985, language=CN, stringName=张雷达, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954122059723243, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, xref=1, ext=[AuthorCompanyExt(id=1322954122068111852, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China), AuthorCompanyExt(id=1322954122076500461, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954118091911646, companyId=1322954122059723243, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆)])])]
唐银, 张捷, 毛毳, 熊涛, 谢传明 , 张雷达
作者信息
  • 1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆
通讯作者:
张雷达；E-mail：
谢传明，E-mail：
ZHANG Leida；E-mail：
XIE Chuanming，E-mail：
High-salt diet promotes the progression of fibrosis in metabolic dysfunction-associated steatohepatitis via activating the PI3K/Akt/mTOR signaling pathway
Yin TANG, Jie ZHANG, Cui MAO, Tao XIONG, Chuanming XIE , Leida ZHANG
Affiliations
  • 1Department of Hepatobiliary Surgery，First Affiliated Hospital（Southwest Hospital），Army Medical University （Third Military Medical University），Chongqing，China
出版时间: 2025-12-30 doi: 10.16016/j.2097-0927.202511049
文章导航
收藏切换
摘要
收起
目的

探究小鼠高脂饮食模型建立的代谢功能障碍相关脂肪性肝炎（metabolic dysfunction-associated steatohepatitis，MASH）在联合高盐饮食背景下对MASH相关肝纤维化进展的影响及潜在的分子机制。

方法

采用C57BL/6J小鼠建立正常饮食小鼠模型、单纯高盐饮食小鼠模型、MASH小鼠模型和MASH联合高盐饮食模型，到达实验终点后取材分别对小鼠肝组织进行苏木素-伊红染色（hematoxylin-eosin staining，H-E）、天狼星红染色（Sirius staining）、免疫组织化学染色（immunohistochemistry，IHC）、油红O染色（Oil Red O）来对小鼠肝脏进行组织学层面评估其脂肪变性程度、脂质沉积及纤维化程度，另外统计分析小鼠肝功和血脂，比较小鼠肝重、体重及其比值变化，对小鼠肝脏组织纤维化标志物及其炎症标志物通过RT-qPCR和Western blot方法进行评估，将肝组织样品送转录组测序后进行生物信息学分析和通过Western blot方法对潜在信号通路进行验证以确认其可能的机制。

结果

通过油红O染色及H&E染色观察可以发现成功建立起代谢功能障碍相关脂肪性肝炎小鼠模型及其联合高盐饮食小鼠模型以及单纯高盐饮食小鼠模型，通过检测血清谷草转氨酶（aspartate transaminase，AST）、谷丙转氨酶（alanine aminotransferase，ALT）、总胆固醇（total cholesterol ，Tch）、甘油三酯（triglyceride，TG）水平可以发现单纯高盐饮食组小鼠在组织学层面与普通饮食组对比无显著差异（P>0.05），而MASH联合高盐饮食组较MASH饮食组AST、ALT水平升高更为显著（P<0.01），表明MASH背景下的高盐饮食可以加重肝损伤；另外通过天狼星红染色、α-SMA免疫组织化学染色发现MASH联合高盐饮食可以加剧MASH相关的肝纤维化（P<0.01），同样MASH联合高盐饮食组在反应纤维化激活相关基因Col1a1、α-SMA、Timp1、Pdgfrβ mRNA水平上表达升高更为显著（P<0.01），MASH联合高盐饮食组α-SMA和Fibronectin蛋白表达水平同样上调更为显著，除此之外反应炎症激活相关基因TNF-α、IL-6、IL-1β、TGF-β1在MASH联合高盐饮食组中表达水平明显上调（P<0.05），表明MASH联合高盐饮食促进了肝炎及肝纤维化发展；转录组测序分析显示PI3K/AKT/mTOR信号通路激活和TGF-β信号上调更为显著，热图显示纤维化和炎症相关基因显著上调；对富集信号通路相关分子进行Western blot实验验证显示MASH联合高盐饮食组的PI3K/AKT/mTOR信号通路显著激活（P<0.01）。

结论

高盐饮食通过PI3K/AKT/mTOR通路激活促进代谢功能障碍相关脂肪性肝炎纤维化进展。

代谢功能障碍相关脂肪性肝炎  /  高盐饮食  /  肝炎  /  肝纤维化  /  PI3K/AKT/mTOR信号通路
Objective

To explore the impact of high-salt diet (HSD) on the progression of high-fat diet (HFD)-induced metabolic dysfunction-associated steatohepatitis (MASH)-related liver fibrosis, as well as the underlying molecular mechanisms.

Methods

C57BL/6J mice were used to establish the following models: normal diet (Chow), HSD diet (Chow+8%salt), MASH diet (MASH), and MASH diet combined with HSD (MASH+8%salt). At the experience endpoint, the liver tissues were collected and subjected to HE staining, Sirius Red staining, immunohistochemistry (IHC) assay, and Oil Red O staining for histological assessment of steatosis, lipid deposition, and fibrosis. The levels of liver function indicators and serum lipids were measured and statistically analyzed, and the differences in liver weight, body weight, and their ratios were compared across the groups. RT-qPCR and Western blotting were applied to detect the mRNA and protein levels of hepatic fibrosis and inflammatory markers. Liver tissue samples were subjected to transcriptome sequencing, followed by bioinformatics analysis. Potential signaling pathways were validated through Western blotting to confirm the underlying mechanisms.

Results

Oil Red O and HE staining confirmed the successful establishment of the mouse models of MASH, MASH+8%salt, and Chow+8%salt. Serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), total cholesterol (Tch), and triglyceride (TG) showed no significant differences between the Chow+8%salt and Chow groups (P>0.05). In contrast, the MASH+8%salt group exhibited significantly higher AST and ALT levels than the MASH group (P<0.01), indicating that HSD exacerbates liver injury in the context of MASH. Sirius Red and α-SMA IHC staining revealed that HSD aggravated MASH-related liver fibrosis (P<0.01). Similarly, the mRNA levels of fibrosis activation-related genes (Col1a1, α-SMA, Timp1, Pdgfrβ) were more significantly up-regulated in the MASH+8%salt group (P<0.01). Protein expression levels of α-SMA and Fibronectin were also markedly elevated. Furthermore, the mRNA levels of inflammation-related genes (TNF-α, IL-6, IL-1β, TGF-β1) were obviously up-regulated in the MASH+8%salt group (P<0.05), suggesting that HSD promotes hepatitis and liver fibrosis progression in MASH. Transcriptome sequencing indicated significant activation of the PI3K/AKT/mTOR signaling pathway and up-regulation of the TGF-β pathway. Heatmap analysis demonstrated marked up-regulation of fibrosis- and inflammation-related genes. Western blotting confirmed significant activation of the PI3K/AKT/mTOR signaling pathway in the MASH+8%salt group (P<0.01).

Conclusion

High-salt diet promotes the progression of hepatitis and liver fibrosis in metabolic dysfunction associated steatohepatitis by activating the PI3K/AKT/mTOR signaling pathway.

metabolic dysfunction-associated steatohepatitis  /  high-salt diet  /  hepatitis  /  liver fibrosis  /  PI3K/AKT/mTOR signaling pathway
唐银, 张捷, 毛毳, 熊涛, 谢传明, 张雷达. 高盐饮食通过PI3K/AKT/mTOR通路激活促进代谢功能障碍相关脂肪性肝炎纤维化进展. 陆军军医大学学报, 2025 , 47 (24) : 3009 -3021 . DOI: 10.16016/j.2097-0927.202511049
Yin TANG, Jie ZHANG, Cui MAO, Tao XIONG, Chuanming XIE, Leida ZHANG. High-salt diet promotes the progression of fibrosis in metabolic dysfunction-associated steatohepatitis via activating the PI3K/Akt/mTOR signaling pathway[J]. Journal of Army Medical University, 2025 , 47 (24) : 3009 -3021 . DOI: 10.16016/j.2097-0927.202511049
正文
收起
代谢功能障碍相关脂肪性肝病（metabolic dysfunction-associated steatotic liver disease ，MASLD）影响了全世界近30%的成年人群，是全球中最常见的慢性肝病之一［1］，特别是肥胖和Ⅱ型糖尿病患者，代谢功能障碍相关脂肪性肝病是一个复杂性的系统性的疾病演变过程，包括了以单纯脂肪变性为主的代谢功能障碍性脂肪肝（metabolic dysfunction-associated fatty liver ，MAFL）到以肝脏脂质积聚、肝细胞气球样变、小叶炎症和不同程度的纤维化为主的代谢功能障碍性脂肪性肝炎（metabolic dysfunction-associated steatohepatitis ，MASH），其持续的肝损伤与修复过程可驱动纤维化进展，最终导致肝硬化、肝功能失代偿和肝细胞癌（hepatocellular carcinoma，HCC）。随着人们生活水平的提高，肥胖、Ⅱ型糖尿病、血脂异常的高发伴随的代谢功能障碍相关脂肪性肝病的发病率逐年提高，代谢功能障碍相关脂肪性肝病不仅仅局限于发达国家，也逐渐成为发展中国家慢性肝病的主要类型。
NaCl，俗称盐，是全球当代饮食中的一种普遍成分，其作为我们日常生活中不可或缺的调味品或防腐剂被添加到膳食中，它在维持我们细胞组织器官及内环境的正常生理过程中发挥着重要作用，但是过量的盐摄入会对我们的身体健康产生负面的影响，过去的研究表明盐摄入过多与心血管疾病发生发展密切相关［2］，有研究显示高盐摄入与肾脏高负荷损伤相关［3］，世界卫生组织膳食指南推荐成人每人每天盐摄入量限制在5 g左右是比较健康的饮食方式［4］，对慢性肝炎病人而言低盐饮食对其是有益的，且临床相关性分析指出高盐饮食与MASH严重程度独立相关［5，6］，而在代谢功能障碍相关脂肪性肝炎背景下高盐饮食对其的影响和作用机制尚不清楚。
现代社会环境下，高效、高压力、快节奏的生活方式往往伴随着不健康的饮食方式和饮食结构，重油、高糖、重盐、饮酒等多重因素的共同影响使该疾病的发展常常表现为多种因素的联合，代谢功能障碍相关脂肪性肝病已经不再仅仅局限于过去单纯的形式和特征。另外一方面，由于我国的不同地区的民族文化和风俗习惯的不同，部分地区盛行熏制腌制食品，盐量摄入较重，更容易形成高盐饮食背景下的代谢功能障碍相关脂肪性肝炎，总体而言，全球的平均盐摄入量仍然很高，平均每天摄入量为12 g，比世界卫生组织建议的每天5 g最高摄入量高出两倍多［7］。因此，对高盐饮食联合代谢功能障碍相关脂肪性肝炎的初步研究旨在找到潜在的分子机制及其靶点，为靶向其纤维化过程及其防治措施提供一定的理论基础。
1　材料与方法
收起
1.1　动物建模
从集萃药康公司购买的6-8周龄的C57BL/6J小鼠进行一周环境适应性饲养后，随机分为四组，每组7只，分别为普通饮食组（Chow）、高盐饮食组（Chow+8%salt）、MASH饮食组（MASH）、MASH加高盐饮食组（MASH+8%salt），饲养于无特定病原体（specific pathogen free，SPF）动物房中。普通饮食组为日粮型食物和普通饮水饲养，高盐饮食组为含8%NaCl的日粮型食物和含0.9%NaCl的饮水饲养，MASH饮食组为MASH饮食和普通饮水饲养，MASH加高盐饮食组为含8%NaCl的MASH饮食和0.9%NaCl的饮水饲养。BABUTA等［8］报道使用一种基于高糖（20.83 gm%）-高脂（33 gm%）-高胆固醇（10 gm%）的饲料可以在12周左右建立起MASH小鼠模型［9］，同时参考既往文献报道一种较为经典的建立高盐饮食模型的方法［10］（以下实验中我们使用MASH模型及其称呼来代表模拟MASLD的整体疾病过程）。因此我们基于此饲料配方联系饲料制作公司（江苏协同）进行饲料定制并分组别饲养建立起小鼠模型，在小鼠饲养过程中定时更换补充饲料和饮水并每隔一周称量记录小鼠体重。以上所有操作符合陆军军医大学动物实验伦理学要求（AMUWEC20252080），实验过程中没有发生与动物有关的不良事件。
1.2　动物取材
到达实验终点后对小鼠取材，眼血取材：小鼠麻醉后使用镊子摘掉眼球，待1.5 mL离心管中收集到合适血液后颈部脱臼处死小鼠，血液于室温静置30 min后3 000 rpm，离心15 min取上清冻存于-80 ℃冰箱，肝组织取材：打开腹腔后，取部分肝组织于冻存管中置于液氮罐中用于下一步实验，剩余肝组织使用10%的福尔马林固定液（sigma-Aldrich，30525-89-4）固定，心、肺、脾、肾、结肠使用福尔马林固定液固定后用于下一步实验。
1.3　组织脱水、包埋与切片
肝组织固定48 h后切取适量组织置于组织包埋盒中，使用组织脱水机（深圳达科为）进行组织脱水（福尔马林30 min、75%乙醇30 min、85%乙醇30 min、95%乙醇30 min、95%乙醇30 min、100%乙醇30 min、100%乙醇30 min、二甲苯30 min、二甲苯30 min、石蜡20 min、石蜡30 min、石蜡40 min），然后使用组织包埋机进行组织包埋，待蜡块冷却后使用组织切片机切出厚度为4 μm的连续组织切片。
1.4　组织脱蜡
将组织切片置于60 ℃烤箱中烘烤2 h后，分别置于二甲苯30 min、二甲苯30 min、100%乙醇5 min、100%乙醇5 min、95%乙醇5 min、95%乙醇5 min、85%乙醇2 min、85%乙醇2 min，以上材料依次脱蜡后置于PBS中洗涤两次，每次5 min，然后置于PBS中。
1.5　小鼠肝功、血脂的测定
将冻存于-80 ℃的血清取出100 μL加入400 μL的生理盐水中混匀后（稀释5倍），送陆军军医大学第一附属医院检验科对谷草转氨酶（Aspartate Transaminase，AST）、谷丙转氨酶（Alanine aminotransferase，ALT）、总胆固醇（Total cholesterol ，Tch）、甘油三酯（triglyceride，TG） 进行检测。
1.6　苏木素伊红（H&E）染色
将脱蜡后的片子放置于苏木素（Solarbio，G1120）染缸中，浸没30 s后，将片子放置于自来水下冲洗反蓝15 min，镜下观察至合适颜色后浸没入伊红（Solarbio，G1120）染液中20 s，稍甩干后浸入无水乙醇中3下，通风橱中晾干后用中性树脂封片，然后置于显微镜下拍照采集图像。
1.7　天狼猩红染色（Sirius Staining）
将脱蜡后的组织切片上滴上适量天狼猩红染液（Merck，CAS#：2610-10-8），完全覆盖住肝组织，置于湿盒中孵育25 min后将片子置于无水乙醇中1 s，通风橱中晾干后中性树脂封片，然后在显微镜下拍照采集图像。
1.8　油红O染色（Oil Red O Staining）
将从液氮罐中取出的肝组织切取一小块置于OCT（樱花OCT冷冻切片包埋剂，Cat#4583）冰冻组织包埋剂里面，然后快速置于液氮中冷却，再置于冰冻切片机上切出5~10 μm的组织切片后使用饱和油红O染色试剂盒进行染色（Solarbio，G1260-100），具体步骤严格按照试剂盒说明书进行操作。
1.9　免疫组织化学（IHC）染色
抗原修复，将脱蜡的切片置于加入了柠檬酸钠抗原修复液（Solarbio，C1032）的PBS溶液中，完全浸没切片，然后置于高压锅中蒸煮，至完全冒大气后2.5 min关闭热源，取出切片后自然降温至室温。使用中衫金桥免疫组织化学试剂盒（中衫金桥，PV-9000）进行染色操作，孵育过氧化物酶封闭30 min，孵育一抗后4 ℃冰箱过夜，第二天PBS洗涤三次，孵育抗体增强液1 h，PBS洗涤三次，室温孵育二抗1 h，PBS洗涤后DAB显影，一抗：α-SMA（proteintech，Cat. #：67735-1-Ig，1∶200）具体步骤严格按照说明书进行操作。
1.10　逆转录实时荧光定量聚合酶链式反应（RT-qPCR）
根据试剂说明书进行实验，Trizol 试剂（TaKaRa，日本）用于从组织或培养细胞中提取总 RNA。使用逆转录试剂盒（TaKaRa，日本）逆转录获取cDNA。然后，采用TB Green（TaKaRa，日本）进行 q-PCR。将上样完毕的96孔PCR板置于实时定量聚合酶链式反应仪器中进行反应，每个样品3个副孔［反应程序：95 ℃，30 s；95 ℃，5 s；60 ℃，30 s（40 次循环），4 ℃］。最后根据 CT结果值和 2-△△Ct 方法来计算基因的相对表达量，所用引物序列见表 1。
1.11　蛋白质免疫印迹实验（Western blot）
用蛋白酶抑制剂混合物（Roche，瑞士）+RIPA 裂解缓冲液（Thermo Fisher，美国）从处理的动物肝组织中提取总蛋白，然后在冰上裂解20 min。裂解后，将裂解液在4 ℃中 13 000 r/min，离心15 min。离心后将上清液收集到新的EP管中。BCA蛋白质试剂盒（Beyotime，中国）用于量化蛋白质的浓度，加入上样缓冲液（Solarbio，中国）。然后金属浴100 ℃，10 min将蛋白变性，变性后将样品通过10％SDS-PAGE 凝胶电泳分离，然后转到NC膜（Amersham，美国）。将膜在室温下用5％脱脂牛奶封闭1 h，然后在4 ℃下与对应一抗孵育过夜。次日，洗膜后将膜与对应种属二抗在室温下孵育1 h后洗膜。使用ECL发光液（雅酶，中国）和凝胶成像系统（BIO-RAD，美国）对蛋白条带进行曝光显影拍照，具体抗体使用及稀释比例见表2。
1.12　肝组织转录组测序
取出液氮冻存的肝组织样本，各切取适量体积组织块，四组每组分别选取3只小鼠样本送美吉生物转录组测序，测序结果依照转录组测序常规方法进行分析。
1.13　细胞培养及处理
LX-2细胞培养后以合适密度铺板，使用PA（棕榈酸：500 μM，KC002，西安鲲创）、NaCl（200 mM）及雷帕霉素（Rapamycin：100 μM，AY-22989，MCE）处理细胞48 h后收样进行蛋白印迹实验，具体参见图4C。
1.14　统计学方法
GraphPad Prism 8. 0 软件用于数据分析和图表制作。计量资料以x¯±s的形式表示。2 组间比较采用双尾非配对t检验。单因素或多因素多个独立组间比较选择单因素方差分析或多因素方差分析。P<0.05认为差异有统计学意义。
2　结果
收起
2.1　高盐饮食会加重MASH饮食小鼠的肝损伤
为了探究代谢功能障碍相关脂肪性肝炎背景下的高盐饮食对肝脏损伤的影响及其病理机制，我们建立了小鼠模型，如方法学中描述，同时给予MASH饮食与高盐饮食3个月（图1A），与普通饮食组相比，MASH饮食组出现显著体重增加，体型更加的肥胖（图1B）；MASH饮食组及MASH加高盐饮食组均出现了代谢功能障碍相关脂肪性肝炎的肝脏大体形态（图1C），而MASH加高盐饮食组的小鼠体重反而较MASH组更低（图1D），尽管如此，MASH加高盐饮食组的小鼠的肝脏大体形态较MASH组更加严重，除了出现了明显的脂肪肝形态外，肝脏出现了不同程度的硬化，边缘变得更加的锐利，表面凸起及颗粒感更加的严重（图1C），且对于肝重体重比值，MASH组较普通饮食组更高，而MASH加高盐饮食组因为肝脏炎症及其硬化较MASH组更低（图1E）。
与普通饮食组相比，MASH饮食组小鼠的肝脏损伤表现为丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平升高（P<0.01，图1H，I）。值得注意的是，与单独MASH饮食或高盐饮食的小鼠相比，高盐饮食进一步加剧了MASH小鼠的转氨酶水平升高，表现为更加严重的肝功能损伤（图1H，I）。
2.2　高盐饮食加速了MASH背景下的肝纤维化和肝炎
通过检测总胆固醇水平（图1F）、甘油三酯水平（图1G）、苏木素-伊红染色切片（图2E）以及油红O染色（图2J），MASH饮食组和MASH联合高盐饮食组均表现出明显的肝脂肪变性特征，大量的脂滴空泡，部分炎症细胞浸润和纤维化结构，显示出了MASH的成功造模结果。
有文献报道，单纯的高盐饮食短时间内对肝纤维化未造成明显的影响，但是在转录组层面上会对肝脏代谢产生一些改变［11］，另外有研究显示单纯高盐饮食与MAFLD的发生相关［12］，也有文献报道高盐饮食可通过Nrf2/Keap1信号产生过量的活性氧（ROS）导致肝损伤［13］，与我们的实验观察一致的是，在组织学层面通过苏木素-伊红（H-E）染色、天狼猩红（Sirius）染色和α-SMA免疫组织化学（IHC）染色上未观察到单纯高盐饮食对肝脏损伤与普通饮食相比有明显差异（图2E，F-I）。为了探究在MASH饮食背景下联合高盐饮食共同造成的肝脏损伤是否会加速纤维化并促进疾病进展，我们通过HE染色、Sirius染色与α-SMA免疫组织化学染色与仅食用MASH饮食或单纯高盐饮食的组相比，同时摄入MASH饮食和高盐饮食的小鼠肝脏纤维化程度更高（P<0.05，图2E，F~I）。
反应肝星状细激活及肝纤维化的标志物，平滑肌肌动蛋白（α-SMA）；细胞外基质标志物及参与基质重塑过程，金属蛋白酶组织抑制剂（Timp1）、I型胶原α1链（Col1a1）以及血小板衍生生长因子受体β（Pdgfrβ）。与对照组、MASH饮食组或单纯高盐饮食组相比，经MASH联合高盐饮食处理的小鼠体内α-SMA、COl1A1、Timp1和PDGFRβ的mRNA水平显著升高（P<0.05，图2A~D）。通过蛋白质印迹法检测发现，α平滑肌肌动蛋白（α-SMA）和粘连蛋白（Fibronectin）等促纤维化标志物在MASH联合高盐饮食组中均呈现显著上调趋势（P<0.01，图2K）。此外，反映炎症水平和促纤维化水平的标志物，白介素6（IL-6）、肿瘤坏死因子α（TNF-α）、白介素1β（IL-1β）和转化生长因子β1（TGF-β1）的mRNA水平除了在MASH饮食组显著升高外，在MASH联合高盐饮食处理小鼠组中升高更为显著（P<0.05，图2L~O）。这些结果表明，高盐饮食会加剧饮食诱导型MASH引发的肝炎和肝纤维化。
2.3　MASH背景下联合高盐饮食的转录组特征
为系统阐明MASH背景下的高盐饮食对促进肝脏炎症及纤维化的潜在机制，我们对MASH饮食及MASH联合高盐饮食肝脏组织进行转录组测序分析以评估MASH联合高盐饮食处理后肝脏转录组变化（每组n=3），通过转录组测序，我们发现MASH联合高盐饮食组与MASH饮食组相比有173个基因显著上调，301个基因显著下调（图3A），基于这些差异表达的基因，KEGG富集分析表明PI3K/AKT/mTOR信号通路、TGF-β炎症信号通路在MASH联合高盐饮食组中具有显著富集（图3B，D，E ），TGF-β是一个强力促纤维化因子，既往文献报道TGF-β可以直接激活PI3K/AKT/mTOR通路［14］，同时PI3K也可以通过调节Smad分子的功能激活TGF-β通路实现正反馈循环通路［15］；进一步热图显示介导炎症、细胞外基质重塑及反应纤维化相关基因表达存在显著改变（图3C）。以上结果表明从转录组层面进一步验证了高盐饮食联合代谢功能障碍相关脂肪性肝炎背景可以进一步导致肝损伤和肝炎及肝纤维化，并主要是通过PI3K/AKT/mTOR信号通路的激活来加速这一过程。
2.4　MASH背景下的高盐饮食通过PI3K/AKT/mTOR信号通路激活加速肝炎及肝纤维化发展
既往文献报道PI3K/AKT/mTOR信号级联在激活HSC中起着至关重要的作用，而肝星状细胞激活是肝纤维化的一个必要步骤［16］。因此，为进一步验证转录组分析结果，在这项研究中，我们对四组小鼠肝组织进行蛋白免疫印迹实验分析以此来确定肝组织中活化AKT （P-AKT）和mTOR （P-mTOR）蛋白以及P-p70S6K的表达水平。与前述结果类似，我们发现在普通饮食组和高盐饮食组中小鼠PI3K/AKT/mTOR激活未见显著差异，与既往报道相一致的是单纯高盐饮食不会对肝功及肝纤维化产生明显的影响［11］，但是MASH饮食组中PI3K/AKT/mTOR激活表达明显上调，而在MASH联合高盐饮食组中该信号通路激活更为显著（图4A、B），为了进一步验证MASH背景下高盐饮食通过PI3K/AKT/mTOR激活发挥的作用，我们在细胞水平上使用棕榈酸（PA）［17］处理肝星状细胞（HSC）模拟高脂饮食，NaCl［18］处理细胞模拟高盐饮食，使用雷帕霉素（Rapamycin）处理细胞来抑制mTOR激活，可以看出NaCl处理可以促进HSC mTOR、AKT激活和α-SMA表达，而联合雷帕霉素处理可以部分逆转此现象（图4C）。此外，mTOR的激活还可以通过磷酸化p70S6K和4EBP1促进核糖体生物合成和蛋白质翻译从而促进纤维化相关基因的蛋白表达水平促进肝纤维化。因此，可以看出，MASH联合高盐饮食通过激活PI3K/AKT/mTOR信号通路加速MASH相关肝炎及肝纤维化的进展。
3　讨论
收起
代谢功能障碍相关脂肪性肝病已成为发达国家乃至许多发展中国家慢性肝病的首要病因，估计影响世界四分之一的人口，构成了巨大的公共卫生负担［19-20］。MASLD的主要特征是肝细胞中脂质沉积、细胞死亡、炎症细胞浸润及纤维化，其常常由于肥胖导致，MASH代表该疾病的中后期阶段，本研究中我们使用文中描述的MASH模型来模拟 MASLD的基本疾病过程。盐是我们日常生活中不可或缺的调味品，适量的摄入对维持生物体内环境的稳定，增强个人体质具有重要的作用，然而过量的盐摄入常常与心血管疾病、肾脏疾病等密切相关［21-23］，既往文献报道肝硬化患者低盐饮食对其生存预后有积极影响［5］，随着社会的发展，快节奏、高效的生活方式往往伴随着不健康的饮食方式和饮食结构，油、糖、盐、酒的摄入失衡使得代谢功能障碍相关脂肪性肝病不再仅仅局限于以西方饮食与肥胖等较为单一因素影响为特征的慢性肝脏疾病，常常表现为多种因素的联合，另外我国的不同地区的民族文化和风俗习惯有所不同，部分地区盛行熏制腌制食品，盐量摄入较重，更容易形成高盐饮食背景下的代谢功能障碍相关脂肪性肝炎，因此，对高盐饮食联合代谢功能障碍相关脂肪性肝炎的初步研究旨在找到潜在的分子机制及其靶点，为靶向其纤维化过程及其防治措施提供一定的理论基础。
既往的研究报道，在MASH中可以通过PI3K/AKT/mTOR信号通路来导致代谢功能障碍相关脂肪性肝炎进展［24-26］ ，肝纤维化过程伴随着PI3K/AKT等信号通路的激活［16，24，28-29］，哺乳动物雷帕霉素靶点（mTOR）作为一种重要的营养感知信号通路，参与了 MASLD 的发生和进展［29-30］ ，mTOR 复合物在氨基酸、葡萄糖、脂质和核酸等丰富营养物质存在下，可以促进合成代谢过程并抑制分解代谢过程［31］。多项研究表明，靶向mTOR的治疗可以缓解 MASLD，既往文献报道使用mTOR抑制剂雷帕霉素可以通过促进肝细胞自噬来减轻脂肪变性、纤维化和炎症［32］。有文献报道在中枢神经系统中高盐饮食可以通过IGF1R/mTOR/p70S6K 信号传导的激活诱发认知功能障碍［33］，另外有文献报道高盐饮食可以激活细胞钠离子通道（ENAc）等影响细胞内钠稳态从而触发多种生长因子信号［34］ ，另外PI3K/AKT/mTOR的激活不仅可以促进TNF-α、IL-6等炎症因子分泌，这几种炎症因子也是PI3K通路的强力激活剂。以上表明PI3K/AKT/mTOR信号通路激活与炎症、纤维化及细胞代谢密切相关，其相互作用形成了共同的调控网络，我们的研究发现单纯MASH饮食和MASH联合高盐饮食条件下，通过PI3K/AKT/mTOR信号通路激活促进肝炎及肝纤维化进展，而MASH联合高盐饮食激活上调更为显著，但单纯高盐饮食与普通饮食组相比，肝组织中PI3K/AKT/mTOR信号通路的激活水平并无显著性差异。
综上所述，本研究证实了在高脂饮食诱导的MASH背景下，叠加高盐饮食可显著促进肝损伤，加速肝炎、肝纤维化进展，其主要通过PI3K/AKT/mTOR信号通路的过度激活导致这一过程，肝脏转录组测序显示细胞外基质重塑，纤维化相关基因表达显著上调，炎症相关基因表达显著上调，Western blot进一步验证了转录组分析结果，细胞水平上也进一步对此结果进行了验证。此研究为MASH背景联合高盐饮食的慢性肝病的人群治疗提供了部分理论依据，在未来，在针对该机制我们可以提出相应的干预方案，针对PI3K及mTOR分子使用相应特异性的抑制剂进行靶向干预，可能对该疾病类型起到一定的缓解作用。本研究的不足之处在于尚未针对潜在的治疗措施在动物水平上进行进一步验证，同时对于临床相关性分析方面也未进行验证，我们将计划收集不同盐摄入水平的MASH患者肝穿刺组织，通过免疫组化或Western blot检测p-AKT和p-mTOR的水平，并与患者的纤维化分期进行相关性分析，以上设想需要未来进一步探索。

文献
收起
参考文献 引证文献
排序方式：
1
HU S，WANG Z X，ZHU K，et al. USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination［J］. Clin Mol Hepatol，2025，31（1）：147-165.
2
NEAL B，WU Y F，FENG X X，et al. Effect of salt substitution on cardiovascular events and death［J］. N Engl J Med，2021，385（12）：1067-1077.
3
JIANG Q，YANG Q F，ZHANG C T，et al. Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats［J］. Respir Res，2024，25（1）：288.
4
CAMPBELL N R C，HE F J，TAN M，et al. The International Consortium for Quality Research on Dietary Sodium/Salt （TRUE） position statement on the use of 24-hour，spot，and short duration （24 hours） timed urine collections to assess dietary sodium intake［J］. J Clin Hypertens （Greenwich），2019，21（6）：700-709.
5
HABERL J，ZOLLNER G，FICKERT P，et al. To salt or not to salt？ -That is the question in cirrhosis［J］. Liver Int，2018，38（7）：1148-1159.
6
KUMAR R，MARRAPU S. Dietary salt in liver cirrhosis：With a pinch of salt！［J］. World J Hepatol，2023，15（10）：1084-1090.
7
POWLES J，FAHIMI S，MICHA R，et al. Global，regional and national sodium intakes in 1990 and 2010：a systematic analysis of 24 h urinary sodium excretion and dietary surveys worldwide［J］. BMJ Open，2013，3（12）：e003733.
8
BABUTA M，MOREL C，DE CARVALHO RIBEIRO M，et al. Neutrophil extracellular traps activate hepatic stellate cells and monocytes via NLRP3 sensing in alcohol-induced acceleration of MASH fibrosis［J］. Gut，2024，73（11）：1854-1869.
9
BABUTA M，NAGESH P T，DATTA A A，et al. Combined insults of a MASH diet and alcohol binges activate intercellular communication and neutrophil recruitment via the NLRP3-IL-1β axis in the liver［J］. Cells，2024，13（11）：960.
10
GAO P，YOU M，LI L，et al. Salt-induced hepatic inflammatory memory contributes to cardiovascular damage through epigenetic modulation of SIRT3［J］. Circulation，2022，145（5）：375-391.
11
LI Y P，LYU Y F，HUANG J，et al. Transcriptome sequencing reveals high-salt diet-induced abnormal liver metabolic pathways in mice［J］. BMC Gastroenterol，2021，21（1）：335.
12
HUH J H，LEE K J，LIM J S，et al. High dietary sodium intake assessed by estimated 24-h urinary sodium excretion is associated with NAFLD and hepatic fibrosis［J］. PLoS One，2015，10（11）：e0143222.
13
WANG G，YEUNG C K，WONG W Y，et al. Liver fibrosis can be induced by high salt intake through excess reactive oxygen species （ROS） production［J］. J Agric Food Chem，2016，64（7）：1610-1617.
14
TANG Q Y，MARKBY G R，MACNAIR A J，et al. TGF-β-induced PI3K/AKT/mTOR pathway controls myofibroblast differentiation and secretory phenotype of valvular interstitial cells through the modulation of cellular senescence in a naturally occurring in vitro canine model of myxomatous mitral valve disease［J］. Cell Prolif，2023，56（6）：e13435.
15
LUO K X. Signaling cross talk between TGF-β/smad and other signaling pathways［J］. Cold Spring Harb Perspect Biol，2017，9（1）：a022137.
16
WANG R，SONG F X，LI S N，et al. Salvianolic acid A attenuates CCl（4）-induced liver fibrosis by regulating the PI3K/AKT/mTOR，Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways［J］. Drug Des Devel Ther，2019，13：1889-1900.
17
XU S W，WU X M，WANG S C，et al. TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase［J］. J Clin Invest，2024，134（5）：e166149.
18
ZHAO K N，LAN Y B，SHI Y，et al. Metabolite and transcriptome analyses reveal the effects of salinity stress on the biosynthesis of proanthocyanidins and anthocyanins in grape suspension cells［J］. Front Plant Sci，2024，15：1351008.
19
NAVARRO-CORCUERA A，ZHU Y W，MA F L，et al. Resolvin D1-mediated cellular crosstalk protects against MASH［J］. JHEP Rep，2025，7（8）：101454.
20
秦嘉怡，周学谦，孟祥勇，等. 瘦型代谢功能障碍相关脂肪性肝病风险预测模型的构建与验证［J］. 陆军军医大学学报，2025，47（9）：969-979.
QIN J Y，ZHOU X Q，MENG X Y，et al. Construction and validation of a risk prediction model for lean metabolic dysfunction-associated steatotic liver disease［J］. J Army Med Univ，2025，47（9）：969-979.
21
SCRIBNER B H. Salt and hypertension［J］. JAMA，1983，250（3）：388.
22
DWYER T. Salt and hypertension ［J］. Med J Aust，1985，142（9）：497-498.
23
SWALES J D. Dietary salt and hypertension［J］. Lancet，1980，315（8179）：1177-1179.
24
LIU R，ZHANG Y，LIU M，et al. Natural molecule isoliquiritigenin mitigates MASH and liver fibrosis in mice by promoting autophagy through the PI3K/Akt signaling pathway［J］. J Nutr Biochem，2025，136：109808.
25
FARRASH W F，IDRIS S，ELZUBIER M E，et al. Enhanced hepatoprotective effects of empagliflozin and vitamin D dual therapy against metabolic dysfunction-associated steatohepatitis in mice by boosted modulation of metabolic，oxidative stress，and inflammatory pathways［J］. Int J Exp Pathol，2024，105（6）：219-234.
26
EZZ-ELDIN Y M，EL-DIN EWEES M G，KHALAF M M，et al. Modulation of SIRT6 related signaling pathways of p-AKT/mTOR and NRF2/HO-1 by memantine contributes to curbing the progression of tamoxifen/HFD-induced MASH in rats［J］. Eur J Pharmacol，2024，984：177069.
27
ZHANG Z L，SHANG J，YANG Q Y，et al. Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism［J］. J Nanobiotechnology，2023，21（1）：29.
28
LI X N，LIU X，SHI X R，et al. REDD1 attenuates cholestatic liver fibrosis and suppresses PI3K/AKT/mTOR pathway［J］. Front Med，2025，12：1628260.
29
GEORGILA K，GOUNIS M，HAVAKI S，et al. mTORC1-dependent protein synthesis and autophagy uncouple in the regulation of Apolipoprotein A-I expression［J］. Metabolism，2020，105：154186.
30
WANG Y G，SHI M，FU H Y，et al. Mammalian target of the rapamycin pathway is involved in non-alcoholic fatty liver disease［J］. Mol Med Rep，2010，3（6）：909-915.
31
SIMCOX J，LAMMING D W. The central moTOR of metabolism［J］. Dev Cell，2022，57（6）：691-706.
32
LEE Y S，PARK J S，LEE D H，et al. The antidiabetic drug lobeglitazone protects mice from lipogenesis-induced liver injury via mechanistic target of rapamycin complex 1 inhibition［J］. Front Endocrinol，2018，9：539.
33
LIU S，YANG X，YUAN M H，et al. High salt diet induces cognitive impairment and is linked to the activation of IGF1R/mTOR/p70S6K signaling［J］. Metab Brain Dis，2024，39（5）：803-819.
34
WANG D，WANG Y，LIU F Q，et al. High salt diet affects renal sodium excretion and ERRα expression［J］. Int J Mol Sci，2016，17（4）：480.
2025年第47卷第24期
PDF下载
16
5
引用本文
BibTeX
文章信息
doi: 10.16016/j.2097-0927.202511049
  • 接收时间：2025-11-10
  • 首发时间：2026-10-30
  • 出版时间：2025-12-30
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2025-11-10
  • 修回日期：2025-11-28
基金
作者信息
    1陆军军医大学（第三军医大学）第一附属医院（西南医院）全军肝胆外科研究所，重庆

通讯作者:

张雷达；E-mail：
谢传明，E-mail：
ZHANG Leida；E-mail：
XIE Chuanming，E-mail：
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/10.16016/j.2097-0927.202511049
分享至
全文二维码

扫描看全文

引用本文
BibTeX
本文的引用情况
2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
相关链接
论文
最新文章
热读文章
热点专题
内参
蓝皮书
产业发展报告
传播力报告
期刊分级目录
资讯
学术新闻
行业新闻
学术会议
行业会议
关于
关于我们
联系我们
北京市海淀区学院南路86号
100081
010-62662699（运营及技术支持）
qkjq@cast.org.cn

中国科学技术协会版权所有 京ICP 备10216604号-4 海淀分局备案 1101084647
科技导报社主办 中国科协信息中心技术支持