Article(id=1322608105830077279, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1322608013010120712, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202506411, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1750694400000, receivedDateStr=2025-06-24, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793263945299, onlineDateStr=2026-10-29, pubDate=1762704000000, pubDateStr=2025-11-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793263945299, onlineIssueDateStr=2026-10-29, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793263945299, creator=13701087609, updateTime=1793263945299, updator=13701087609, issue=Issue{id=1322608013010120712, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='21', pageStart='3841', pageEnd='4032', issueExtLink='null', onlineDate='null', pubDate='1762704000000', pubDateStr='2025-11-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793263923169, creator='13701087609', updateTime=1793264266929, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322609454932149086, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1322608013010120712, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322609454932149087, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1322608013010120712, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=4001, endPage=4008, ext={EN=ArticleExt(id=1322608106023015264, articleId=1322608105830077279, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Network pharmacology and experimental validation of β-carotene in alleviating hyperuricemic renal injury via suppressing NLRP3 inflammasome activation, columnId=1228016572065837304, journalTitle=Modern Preventive Medicine, columnName=Experimental Technology and Applications, runingTitle=null, highlight=null, articleAbstract=
Objective To explore the potential targets and mechanisms of β-carotene in the treatment of hyperuricemia (HUA) by integrating network pharmacology analysis with in vivo mouse experiments.
Methods Targets related to β-carotene were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), CTDbase, and Swiss Target Prediction databases. Therapeutic targets for HUA were obtained from the GeneCards, DigSee, and DisGeNET databases. Venn diagram analysis was used to identify overlapping targets between β-carotene-related targets and HUA disease targets, and a protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the identified overlapping targets. C57BL/6 mice were divided into 5 groups: normal group, HUA (model group), positive control allopurinol (62.5 mg/kg) group, 20 mg/kg β-carotene group, and 40 mg/kg β-carotene group. Except for the control group, all other groups were induced to establish the HUA mouse model using potassium oxonate and hypoxanthine. Serum levels of uric acid (UA), urea nitrogen (BUN), and creatinine (CRE) were measured using biochemical assay kits. Renal tissue injury was observed using hematoxylin-eosin (H&E) staining.Levels of interleukin-1β (IL-1β) and IL-18 were detected using enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used to detect protein expression levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and cleaved Caspase-1. Immunohistochemical staining was used to observe NLRP3 expression levels in renal tissue.
Results Matching 254 β-carotene-related targets with 170 HUA-related targets yielded 15 overlapping β-carotene-HUA target genes. KEGG enrichment indicated that β-carotene primarily treated HUA by involving inflammation and apoptosis pathways, with NLRP3 inflammasome enrichment being the most significant. Compared to the model group, both 20 mg/kg β-carotene and 40 mg/kg β-carotene significantly reduced serum UA (F=119.3, P<0.01), BUN (F=112.7, P<0.01), and CRE (F=80.76, P<0.01) levels in HUA mice, alleviated renal injury, decreased renal tissue levels of IL-1β (F=97.8, P<0.01) and IL-18(F=137.0, P<0.01), and downregulated the expression levels of NLRP3 (F=178.4, P<0.01), ASC (F=392.5, P<0.01), and cleaved-Caspase-1 (F=171.6, P<0.01).
Conclusion β-Carotene can alleviate renal injury and reduce inflammatory responses in HUA mice. Its mechanism may be associated with inhibiting the activation of the NLRP3 inflammasome.
, authors=Ying-pei DU
1, Wei-wei WANG
1, Zhen-kun LU
2, Jia-ying ZHOU
2, authorsList=Ying-pei DU, Wei-wei WANG, Zhen-kun LU, Jia-ying ZHOU, authorCompany=null, correspAuthors=Jia-ying ZHOU, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, 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=1322608109621728111, articleId=1322608105830077279, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=网络药理学联合实验验证β-胡萝卜素抑制NLRP3炎症小体活化改善高尿酸血症肾损伤, columnId=1228016572288135432, journalTitle=现代预防医学, columnName=实验技术及其应用, runingTitle=null, highlight=null, articleAbstract=
目的 利用网络药理学结合小鼠高尿酸血症(hyperuricemia,HUA)模型验证,探索β-胡萝卜素治疗HUA的潜在作用靶点及机制。
方法 利用中药系统药理学数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology Database,TCMSP)、CTDbase和Swiss Target Prediction数据库获取β-胡萝卜素的相关靶点,在GeneCards、Digsee和DisGeNET数据库中获取HUA治疗靶点。通过维恩图分析获得β-胡萝卜素相关靶点与HUA疾病靶点的重叠靶点,构建蛋白质-蛋白质相互作用(protein-protein interactions,PPI)网络。对所得交集靶点进行基因本体(gene ontology,GO)与京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析。C57BL/6小鼠分为五组:正常组、HUA(模型组)、阳性药别嘌醇(62.5 mg/kg)组、20 mg/kg β-胡萝卜素组和40 mg/kg β-胡萝卜素组。除正常组外,所有组均用氧嗪酸钾和次黄嘌呤诱导构建HUA模型。采用生化试剂盒测定血清尿酸、尿素氮和肌酐水平。用苏木精-伊红(hematoxylin-eosin,HE)染色法观察肾组织损伤情况。应用酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)试剂盒检测白介素-1β(interleukin-1 β,IL-1β)和IL-18的水平。采用western blot检测NOD样受体蛋白3(NOD-like receptor protein 3,NLRP3)、凋亡相关斑点样蛋白(apoptosis-related spotted protein,ASC)和活化的半胱氨酸天冬氨酸蛋白酶-1(cleaved-Caspase-1)蛋白表达水平。免疫组织化学染色法观察肾组织中NLRP3表达水平。
结果 通过254个β-胡萝卜素相关靶点和170个HUA相关靶点的匹配,得到15个重叠靶点基因。KEGG富集结果显示,β-胡萝卜素治疗HUA主要涉及炎症和细胞凋亡通路,其中NLRP3炎性小体富集最显著。与模型组相比,20 mg/kg β-胡萝卜素和40 mg/kg β-胡萝卜素均显著降低HUA小鼠血清尿酸(F=119.3,P<0.01)、尿素氮(F=112.7,P<0.01)和肌酐(F=80.76,P<0.01)水平,减轻HUA小鼠肾脏损伤,降低肾组织中IL-1β(F=97.8,P<0.01)和IL-18(F=137.0,P<0.01)水平,下调NLRP3(F=178.4,P<0.01)、ASC(F=392.5,P<0.01)和cleaved-Caspase1(F=171.6,P<0.01)表达水平。
结论 β-胡萝卜素减轻HUA小鼠肾脏损伤,降低炎性反应,其机制可能与抑制NLRP3炎症小体的活化有关。
, authors=杜瑛培
1, 王薇薇
1, 卢震坤
2, 周佳莹
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杜瑛培(1988—),女,硕士,主管药师,研究方向:药理学
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本刊刊出的所有文章不代表中华预防医学会和本刊编委会的观点,除非特别声明。, copyrightOwner=中华预防医学会和四川大学华西公共卫生学院, extLink=null, articleAbsUrl=null, sourceXml=Twx7W8o/mxXZ4dVC8WWQ+g==, magXml=mykXmtgRUbHhvGO4EXEptw==, pdfUrl=null, pdf=kKCjbwtfXF+S6JCz/N8w4A==, pdfFileSize=1608105, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=T4AFo8vegSEJnuRtZibiaQ==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=Dp+0doNRT501nuaq97wWMg==, mapNumber=null, fund=null)}, authors=[Author(id=1322608110099878774, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, 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=1322608110196347768, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, authorId=1322608110099878774, language=EN, stringName=Ying-pei DU, firstName=Ying-pei, middleName=null, lastName=DU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=
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18 (3): 403., articleTitle=Carotenoids for antiaging: nutraceutical, pharmaceutical, and cosmeceutical applications, refAbstract=null)], funds=[Fund(id=1322608114902356896, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, awardId=2019JZZY011121, language=CN, fundingSource=山东省重大科技创新工程项目(2019JZZY011121), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1322608109881774960, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, xref=1., ext=[AuthorCompanyExt(id=1322608109890163569, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, companyId=1322608109881774960, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Pharmacy, The Eighth People’s Hospital of Qingdao, Qingdao, Shandong 266000, China), AuthorCompanyExt(id=1322608109898552178, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, companyId=1322608109881774960, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=
1.青岛市第八人民医院药学部,山东 青岛 266000)]), AuthorCompany(id=1322608109974049651, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, xref=2., ext=[AuthorCompanyExt(id=1322608110007604084, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, companyId=1322608109974049651, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=
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Intersection of β-Carotene targets and HUA disease targets, figureFileSmall=ZWG4+yqfhxY/SrLrlW+1tQ==, figureFileBig=T4AFo8vegSEJnuRtZibiaQ==, tableContent=null), ArticleFig(id=1322608113623094165, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, language=CN, label=图1, caption=
β-胡萝卜素作用靶点与HUA疾病靶点交集, figureFileSmall=ZWG4+yqfhxY/SrLrlW+1tQ==, figureFileBig=T4AFo8vegSEJnuRtZibiaQ==, tableContent=null), ArticleFig(id=1322608113837003670, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, language=EN, label=Figure 2, caption=
PPI network of target proteins, figureFileSmall=WMmu3nFMcrnfk9+pvBJd2Q==, figureFileBig=T8Rb3QzUNvu1DMgmFgUFjg==, tableContent=null), ArticleFig(id=1322608114071884695, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, language=CN, label=图2, caption=
靶点蛋白PPI网络注:ALB为白蛋白;PTGS2为环氧酶2。
, figureFileSmall=WMmu3nFMcrnfk9+pvBJd2Q==, figureFileBig=T8Rb3QzUNvu1DMgmFgUFjg==, tableContent=null), ArticleFig(id=1322608114138993560, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, language=EN, label=Figure 3, caption=
Enrichment analysis, figureFileSmall=ZBMOuunUBarRi8pxHT037Q==, figureFileBig=Jc3BrXfxdpSCiBuak/A9MA==, tableContent=null), ArticleFig(id=1322608114214491033, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, language=CN, label=图3, caption=
富集分析注:图A为GO基因生物过程富集;图B为GO细胞成分富集;图C为GO分子功能富集;图D为KEGG信号通路富集。
, figureFileSmall=ZBMOuunUBarRi8pxHT037Q==, figureFileBig=Jc3BrXfxdpSCiBuak/A9MA==, tableContent=null), ArticleFig(id=1322608114428400538, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, language=EN, label=Figure 4, caption=
Effects of β-Carotene on serum UA, CRE, BUN and inflammatory cytokines in HUA mice, figureFileSmall=3d2hrmmukQ5tvWEBbHy62w==, figureFileBig=BP52OV5m5ztvugCdnmH9Uw==, tableContent=null), ArticleFig(id=1322608114491315099, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, language=CN, label=图4, caption=
β-胡萝卜素对HUA小鼠血清尿酸、肌酐和尿素氮及炎性因子水平的影响注:图A血清尿酸水平;图B血清肌酐水平;图C血尿尿素氮水平;图D ELISA检测肾组织中IL-1β水平;图E 肾组织中IL-18水平;与正常组相比,**P<0.01;与模型组相比,#P<0.05,##P<0.01。
, figureFileSmall=3d2hrmmukQ5tvWEBbHy62w==, figureFileBig=BP52OV5m5ztvugCdnmH9Uw==, tableContent=null), ArticleFig(id=1322608114562618268, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, language=EN, label=Figure 5, caption=
Effect of β-Carotene on renal histopathology in HUA mice, figureFileSmall=QywvcCrW1SDpiW9fS8uWTg==, figureFileBig=or7Q2vJO+FmbwMO/8qdwSQ==, tableContent=null), ArticleFig(id=1322608114638115741, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, language=CN, label=图5, caption=
β-胡萝卜素对HUA小鼠肾脏组织病理学变化的影响注:图A小鼠肾组织;图B肾组织HE染色(×200);绿色圈代表肾小球,黑色箭头代表肾小管。
, figureFileSmall=QywvcCrW1SDpiW9fS8uWTg==, figureFileBig=or7Q2vJO+FmbwMO/8qdwSQ==, tableContent=null), ArticleFig(id=1322608114709418910, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, language=EN, label=Figure 6, caption=
Effect of β-Carotene on NLRP3 inflammasome activation, figureFileSmall=jotaTN5dMtk7WnaPl/UnAQ==, figureFileBig=9Ghv3kj+WAh2eq8ZLnyqMA==, tableContent=null), ArticleFig(id=1322608114797499295, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1322608105830077279, language=CN, label=图6, caption=
β-胡萝卜素对NLRP3炎症小体激活的影响注:图A免疫组化染色法检测肾组织中NLRP3表达水平图(×200);图B NLRP3蛋白阳性染色百分比;图C Western blot检测肾组织中NLRP3、ASC和cleaved-Caspase1的表达水平;图D蛋白表达量灰度比值;与正常组相比,**P<0.01;与模型组相比,#P<0.05,##P<0.01。
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