首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1241022579528487756, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241022576185634950, articleNumber=null, orderNo=null, doi=10.14109/j.cnki.xyylc.2024.09.02, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1699545600000, receivedDateStr=2023-11-10, revisedDate=null, revisedDateStr=null, acceptedDate=1724256000000, acceptedDateStr=2024-08-22, onlineDate=1773812440044, onlineDateStr=2026-03-18, pubDate=1727193600000, pubDateStr=2024-09-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773812440044, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773812440044, creator=13701087609, updateTime=1773812440044, updator=13701087609, issue=Issue{id=1241022576185634950, tenantId=1146029695717560320, journalId=1205117082300743687, year='2024', volume='43', issue='9', pageStart='641', pageEnd='720', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773812439247, creator=13701087609, updateTime=1773813972032, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241029005206417725, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241022576185634950, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241029005206417726, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241022576185634950, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=646, endPage=650, ext={EN=ArticleExt(id=1241022580031804239, articleId=1241022579528487756, tenantId=1146029695717560320, journalId=1205117082300743687, language=EN, title=Research progress on mechanism of sodium-glucose cotransporter 2 inhibitors against podocyte damage, columnId=1207314219599499390, journalTitle=Chinese Journal of New Drugs and Clinical Remedies, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Chronic kidney disease is a global public health problem, which can progress to end-stage kidney disease. Podocyte injury is a common pathological type of various glomerular diseases, and the incidence of proteinuria can increase with the decrease of podocyte number. The treatment of podocyte injury is still limited by complex etiology, significant side effects of immunotherapy, and late initiation of targeted non-immunosuppressive therapy. In recent years, the research on the mechanism of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in chronic kidney disease had become increasingly extensive and in-depth, but there were still few reports on targeting podocytes. In this paper, the mechanism of SGLT2i against podocyte injury is reviewed, which provides a more sufficient theoretical foundation for the application of SGLT2i in the treatment of podocyte injury-related diseases.

, correspAuthors=null, 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, authorCompany=null, fund=null, authors=null, authorsList=Wei HUAN, Xiao LI, Wen-juan HONG, Xiao-fei LUO, Jia-mao CHENG), CN=ArticleExt(id=1241022580388320083, articleId=1241022579528487756, tenantId=1146029695717560320, journalId=1205117082300743687, language=CN, title=钠-葡萄糖共转运蛋白2抑制剂抗足细胞损伤机制研究进展, columnId=1207314219767271558, journalTitle=中国新药与临床杂志, columnName=综述, runingTitle=null, highlight=null, articleAbstract=

慢性肾脏病是一个全球性的公共卫生问题，可进展为终末期肾脏病。足细胞损伤是多种肾小球疾病常见的病理类型，蛋白尿的发生可随足细胞数量的减少而增加。足细胞损伤的治疗仍受到病因复杂、免疫治疗副作用大、非免疫抑制靶向治疗起步晚等诸多限制。近年来，关于钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）在慢性肾脏病中的作用机制研究越来越广泛而深入，但以足细胞为靶点的研究报道仍较少。本文综述SGLT2i抗足细胞损伤机制，以期为SGLT2i在治疗足细胞损伤相关性疾病中的应用提供更充分的理论支持。

, correspAuthors=null, authorNote=null, correspAuthorsNote=
李潇，E-mail：
成家茂，E-mail：
, copyrightStatement=null, copyrightOwner=《中国新药与临床杂志》编辑部, extLink=null, articleAbsUrl=null, sourceXml=or99vmE94Ri1dhOpDMkQyw==, magXml=2T7jce4IE8+RVo8iiXkkwA==, pdfUrl=null, pdf=P/6LQUctSPatYCsLpkYGTw==, pdfFileSize=1806217, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=T0xSSZ93ChsOdrOIOXIG/g==, mapNumber=null, authorCompany=null, fund=null, authors=

环薇，女，硕士在读，主要从事肾脏疾病的研究，E-mail：

, authorsList=环薇, 李潇, 洪文娟, 罗晓菲, 成家茂)}, authors=[Author(id=1241029115453689856, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=962542824@qq.com, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1241029115516604418, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, authorId=1241029115453689856, language=EN, stringName=Wei HUAN, firstName=Wei, middleName=null, lastName=HUAN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.Clinical Medical College of Dali University, Dali YUNNAN 671003, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241029115625656325, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, authorId=1241029115453689856, language=CN, stringName=环薇, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.大理大学临床医学院，云南 大理　671003, bio={"content":"

环薇，女，硕士在读，主要从事肾脏疾病的研究，E-mail：

"}, bioImg=null, bioContent=

环薇，女，硕士在读，主要从事肾脏疾病的研究，E-mail：

, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241029115239781367, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, xref=1., ext=[AuthorCompanyExt(id=1241029115252364280, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115239781367, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Clinical Medical College of Dali University, Dali YUNNAN 671003, China), AuthorCompanyExt(id=1241029115260752889, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115239781367, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.大理大学临床医学院，云南 大理　671003)])]), Author(id=1241029115692765194, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=176502468@qq.com, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1241029115759874064, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, authorId=1241029115692765194, language=EN, stringName=Xiao LI, firstName=Xiao, middleName=null, lastName=LI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2.Department of Nephrology, the First Affiliated Hospital of Dali University, Dali YUNNAN 671013, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241029115818594324, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, authorId=1241029115692765194, language=CN, stringName=李潇, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2.大理大学第一附属医院 肾脏内科，云南 大理　671013, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241029115315278842, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, xref=2., ext=[AuthorCompanyExt(id=1241029115319473147, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115315278842, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.Department of Nephrology, the First Affiliated Hospital of Dali University, Dali YUNNAN 671013, China), AuthorCompanyExt(id=1241029115327861756, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115315278842, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.大理大学第一附属医院 肾脏内科，云南 大理　671013)])]), Author(id=1241029115952812055, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, 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=1241029116036698140, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, authorId=1241029115952812055, language=EN, stringName=Wen-juan HONG, firstName=Wen-juan, middleName=null, lastName=HONG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2.Department of Nephrology, the First Affiliated Hospital of Dali University, Dali YUNNAN 671013, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241029116120584225, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, authorId=1241029115952812055, language=CN, stringName=洪文娟, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2.大理大学第一附属医院 肾脏内科，云南 大理　671013, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241029115315278842, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, xref=2., ext=[AuthorCompanyExt(id=1241029115319473147, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115315278842, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.Department of Nephrology, the First Affiliated Hospital of Dali University, Dali YUNNAN 671013, China), AuthorCompanyExt(id=1241029115327861756, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115315278842, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.大理大学第一附属医院 肾脏内科，云南 大理　671013)])]), Author(id=1241029116183498786, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, 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=1241029116258996262, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, authorId=1241029116183498786, language=EN, stringName=Xiao-fei LUO, firstName=Xiao-fei, middleName=null, lastName=LUO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.Clinical Medical College of Dali University, Dali YUNNAN 671003, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241029117727002665, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, authorId=1241029116183498786, language=CN, stringName=罗晓菲, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.大理大学临床医学院，云南 大理　671003, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241029115239781367, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, xref=1., ext=[AuthorCompanyExt(id=1241029115252364280, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115239781367, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Clinical Medical College of Dali University, Dali YUNNAN 671003, China), AuthorCompanyExt(id=1241029115260752889, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115239781367, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.大理大学临床医学院，云南 大理　671003)])]), Author(id=1241029117819277357, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, orderNo=4, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=chjmao@163.com, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1241029117894774834, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, authorId=1241029117819277357, language=EN, stringName=Jia-mao CHENG, firstName=Jia-mao, middleName=null, lastName=CHENG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=3, address=3.Department of Human Anatomy, Basic Medical College of Dali University, Dali YUNNAN 671003, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241029117995438135, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, authorId=1241029117819277357, language=CN, stringName=成家茂, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=3, address=3.大理大学基础医学院 解剖教研室，云南 大理　671003, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241029115386582013, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, xref=3., ext=[AuthorCompanyExt(id=1241029115390776318, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115386582013, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.Department of Human Anatomy, Basic Medical College of Dali University, Dali YUNNAN 671003, China), AuthorCompanyExt(id=1241029115399164927, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115386582013, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.大理大学基础医学院 解剖教研室，云南 大理　671003)])])], keywords=[Keyword(id=1241029118154821693, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, language=EN, orderNo=1, keyword=sodium-glucose cotransporter 2 inhibitors), Keyword(id=1241029118242902082, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, language=EN, orderNo=2, keyword=kidney failure), Keyword(id=1241029118318399558, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, language=EN, orderNo=3, keyword=podocytes), Keyword(id=1241029118435840077, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, language=EN, orderNo=4, keyword=chronic kidney disease), Keyword(id=1241029118486171728, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, language=CN, orderNo=1, keyword=钠-葡萄糖共转运蛋白2抑制剂), Keyword(id=1241029118549086291, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, language=CN, orderNo=2, keyword=肾功能衰竭), Keyword(id=1241029118616195159, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, language=CN, orderNo=3, keyword=足细胞), Keyword(id=1241029118708469851, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, language=CN, orderNo=4, keyword=慢性肾脏病)], refs=[Reference(id=1241029119174037630, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=38, issue=5, pageStart=453, pageEnd=464, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=上海市肾内科临床质量控制中心专家组, journalName=中华肾脏病杂志, refType=null, unstructuredReference=上海市肾内科临床质量控制中心专家组. 慢性肾脏病早期筛查、诊断及防治指南（2022年版）[J]. 中华肾脏病杂志, 2022, 38（5）: 453-464., articleTitle=慢性肾脏病早期筛查、诊断及防治指南（2022年版）, refAbstract=null), Reference(id=1241029119362781316, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=38, issue=5, pageStart=453, pageEnd=464, url=null, language=null, rfNumber=[1], rfOrder=1, authorNames=Expert Group on Kidney Clinical Quality Control Center in Shanghai, journalName=Chin J Nephrol, refType=null, unstructuredReference=Expert Group on Kidney Clinical Quality Control Center in Shanghai. Guidelines for early screening, diagnosis, prevention and treatment of chronic kidney disease （2022 Edition）[J]. Chin J Nephrol, 2022, 38（5）: 453-464., articleTitle=Guidelines for early screening, diagnosis, prevention and treatment of chronic kidney disease （2022 Edition）, refAbstract=null), Reference(id=1241029119463444616, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2020, volume=21, issue=5, pageStart=1559, pageEnd=null, url=null, language=null, rfNumber=[2], rfOrder=2, authorNames=LI G, KIDD J, LI PL, journalName=Int J Mol Sci, refType=null, unstructuredReference=LI G, KIDD J, LI PL. Podocyte lysosome dysfunction in chronic glomerular diseases [J]. Int J Mol Sci, 2020, 21（5）: 1559., articleTitle=Podocyte lysosome dysfunction in chronic glomerular diseases, refAbstract=null), Reference(id=1241029119530553485, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2021, volume=38, issue=5, pageStart=2201, pageEnd=2212, url=null, language=null, rfNumber=[3], rfOrder=3, authorNames=MIMA A, journalName=Adv Ther, refType=null, unstructuredReference=MIMA A. Sodium-glucose cotransporter2 inhibitors in patients with non-diabetic chronic kidney disease [J]. Adv Ther, 2021, 38（5）:2201-2212., articleTitle=Sodium-glucose cotransporter2 inhibitors in patients with non-diabetic chronic kidney disease, refAbstract=null), Reference(id=1241029119631216786, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2021, volume=1, issue=1, pageStart=21, pageEnd=33, url=null, language=null, rfNumber=[4], rfOrder=4, authorNames=MIYATA KN, ZHANG SL, CHAN JSD, journalName=Glomerular Dis, refType=null, unstructuredReference=MIYATA KN, ZHANG SL, CHAN JSD. The rationale and evidence for SGLT2 inhibitors as a treatment for nondiabetic glomerular disease [J]. Glomerular Dis, 2021, 1（1）: 21-33., articleTitle=The rationale and evidence for SGLT2 inhibitors as a treatment for nondiabetic glomerular disease, refAbstract=null), Reference(id=1241029119723491477, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2018, volume=3, issue=15, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[5], rfOrder=5, authorNames=CASSIS P, LOCATELLI M, CERULLO D, journalName=JCI Insight, refType=null, unstructuredReference=CASSIS P, LOCATELLI M, CERULLO D, et al. SGLT2 inhibitor dapagliflozin limits podocyte damage in proteinuric nondiabetic nephropathy [J]. JCI Insight, 2018, 3（15）: e98720., articleTitle=SGLT2 inhibitor dapagliflozin limits podocyte damage in proteinuric nondiabetic nephropathy, refAbstract=null), Reference(id=1241029119786406045, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2018, volume=47, issue=Suppl 1, pageStart=3, pageEnd=13, url=null, language=null, rfNumber=[6], rfOrder=6, authorNames=GARG P, journalName=Am J Nephrol, refType=null, unstructuredReference=GARG P. A review of podocyte biology [J]. Am J Nephrol, 2018,47 Suppl 1 : 3-13., articleTitle=A review of podocyte biology, refAbstract=null), Reference(id=1241029119895457957, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2020, volume=6, issue=1, pageStart=68, pageEnd=null, url=null, language=null, rfNumber=[7], rfOrder=7, authorNames=KOPP JB, ANDERS HJ, SUSZTAK K, journalName=Nat Rev Dis Primers, refType=null, unstructuredReference=KOPP JB, ANDERS HJ, SUSZTAK K, et al. Podocytopathies [J]. Nat Rev Dis Primers, 2020, 6（1）: 68., articleTitle=Podocytopathies, refAbstract=null), Reference(id=1241029119991926954, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2021, volume=320, issue=5, pageStart=F922, pageEnd=F933, url=null, language=null, rfNumber=[8], rfOrder=8, authorNames=OKABE M, YAMAMOTO K, MIYAZAKI Y, journalName=Am J Physiol Renal Physiol, refType=null, unstructuredReference=OKABE M, YAMAMOTO K, MIYAZAKI Y, et al. Indirect podocyte injury manifested in a partial podocytectomy mouse model[J]. Am J Physiol Renal Physiol, 2021, 320（5）: F922-F933., articleTitle=Indirect podocyte injury manifested in a partial podocytectomy mouse model, refAbstract=null), Reference(id=1241029120084201648, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=7, issue=7, pageStart=1463, pageEnd=1476, url=null, language=null, rfNumber=[9], rfOrder=9, authorNames=YAU K, DHARIA A, ALROWIYTI I, journalName=Kidney Int Rep, refType=null, unstructuredReference=YAU K, DHARIA A, ALROWIYTI I, et al. Prescribing SGLT2 inhibitors in patients with CKD: expanding indications and practical considerations[J]. Kidney Int Rep, 2022, 7（7）: 1463-1476., articleTitle=Prescribing SGLT2 inhibitors in patients with CKD: expanding indications and practical considerations, refAbstract=null), Reference(id=1241029120163893429, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=22, issue=1, pageStart=39, pageEnd=52, url=null, language=null, rfNumber=[10], rfOrder=10, authorNames=BAILEY CJ, DAY C, BELLARY S, journalName=Curr Diab Rep, refType=null, unstructuredReference=BAILEY CJ, DAY C, BELLARY S. Renal protection with SGLT2 inhibitors: effects in acute and chronic kidney disease [J]. Curr Diab Rep, 2022, 22（1）: 39-52., articleTitle=Renal protection with SGLT2 inhibitors: effects in acute and chronic kidney disease, refAbstract=null), Reference(id=1241029120247779512, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=13, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[11], rfOrder=11, authorNames=GUO R, WANG P, ZHENG X, journalName=Front Pharmacol, refType=null, unstructuredReference=GUO R, WANG P, ZHENG X, et al. SGLT2 inhibitors suppress epithelial-mesenchymal transition in podocytes under diabetic conditions via downregulating the IGF1R/PI3K pathway [J]. Front Pharmacol, 2022, 13 : 897167., articleTitle=SGLT2 inhibitors suppress epithelial-mesenchymal transition in podocytes under diabetic conditions via downregulating the IGF1R/PI3K pathway, refAbstract=null), Reference(id=1241029120327471293, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=11, issue=23, pageStart=3913, pageEnd=null, url=null, language=null, rfNumber=[12], rfOrder=12, authorNames=CHEN X, WANG J, LIN Y, journalName=Cells, refType=null, unstructuredReference=CHEN X, WANG J, LIN Y, et al. Signaling pathways of podocyte injury in diabetic kidney disease and the effect of sodium-glucose cotransporter 2 inhibitors[J]. Cells, 2022, 11（23）: 3913., articleTitle=Signaling pathways of podocyte injury in diabetic kidney disease and the effect of sodium-glucose cotransporter 2 inhibitors, refAbstract=null), Reference(id=1241029120419745988, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=37, issue=5, pageStart=847, pageEnd=859, url=null, language=null, rfNumber=[13], rfOrder=13, authorNames=HUDKINS KL, LI X, HOLLAND AL, journalName=Nephrol Dial Transplant, refType=null, unstructuredReference=HUDKINS KL, LI X, HOLLAND AL, et al. Regression of diabetic nephropathy by treatment with empagliflozin in BTBR ob/ob mice[J]. Nephrol Dial Transplant, 2022, 37（5）: 847-859., articleTitle=Regression of diabetic nephropathy by treatment with empagliflozin in BTBR ob/ob mice, refAbstract=null), Reference(id=1241029120528797896, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2021, volume=8, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[14], rfOrder=14, authorNames=FONSECA-CORREA JI, CORREA-ROTTER R, journalName=Front Med （Lausanne）, refType=null, unstructuredReference=FONSECA-CORREA JI, CORREA-ROTTER R. Sodium-glucose cotransporter 2 inhibitors mechanisms of action: a review [J]. Front Med （Lausanne）, 2021, 8 : 777861., articleTitle=Sodium-glucose cotransporter 2 inhibitors mechanisms of action: a review, refAbstract=null), Reference(id=1241029120650432718, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=12, issue=1, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[15], rfOrder=15, authorNames=TIAN Y, CHEN XM, LIANG XM, journalName=Sci Rep, refType=null, unstructuredReference=TIAN Y, CHEN XM, LIANG XM, et al. SGLT2 inhibitors attenuate nephrin loss and enhance TGF-β1secretion in type 2 diabetes patients with albuminuria: a randomized clinical trial [J]. Sci Rep,2022, 12（1）: 15695., articleTitle=SGLT2 inhibitors attenuate nephrin loss and enhance TGF-β1secretion in type 2 diabetes patients with albuminuria: a randomized clinical trial, refAbstract=null), Reference(id=1241029120730124495, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=90, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[16], rfOrder=16, authorNames=YANG L, LIANG B, LI J, journalName=Cell Signal, refType=null, unstructuredReference=YANG L, LIANG B, LI J, et al. Dapagliflozin alleviates advanced glycation end product induced podocyte injury through AMPK/mTOR mediated autophagy pathway[J]. Cell Signal, 2022, 90 :110206., articleTitle=Dapagliflozin alleviates advanced glycation end product induced podocyte injury through AMPK/mTOR mediated autophagy pathway, refAbstract=null), Reference(id=1241029122231685335, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=156, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[17], rfOrder=17, authorNames=AHMADIAN E, EFTEKHARI A, ATAKISHIZADA S, journalName=Biomed Pharmacother, refType=null, unstructuredReference=AHMADIAN E, EFTEKHARI A, ATAKISHIZADA S, et al. Podocytopathy: the role of actin cytoskeleton [J]. Biomed Pharmacother, 2022, 156 : 113920., articleTitle=Podocytopathy: the role of actin cytoskeleton, refAbstract=null), Reference(id=1241029122319765723, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2020, volume=11, issue=12, pageStart=596, pageEnd=610, url=null, language=null, rfNumber=[18], rfOrder=18, authorNames=KLIMONTOV VV, KORBUT AI, TASKAEVA IS, journalName=World J Diabetes, refType=null, unstructuredReference=KLIMONTOV VV, KORBUT AI, TASKAEVA IS, et al. Empagliflozin alleviates podocytopathy and enhances glomerular nephrin expression indb/dbdiabetic mice[J]. World J Diabetes,2020, 11（12）: 596-610., articleTitle=Empagliflozin alleviates podocytopathy and enhances glomerular nephrin expression indb/dbdiabetic mice, refAbstract=null), Reference(id=1241029122424623328, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2017, volume=2017, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[19], rfOrder=19, authorNames=DAI H, LIU Q, LIU B, journalName=J Diabetes Res, refType=null, unstructuredReference=DAI H, LIU Q, LIU B. Research progress on mechanism of podocyte depletion in diabetic nephropathy [J]. J Diabetes Res, 2017, 2017:2615286., articleTitle=Research progress on mechanism of podocyte depletion in diabetic nephropathy, refAbstract=null), Reference(id=1241029122521092322, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2017, volume=39, issue=1, pageStart=474, pageEnd=483, url=null, language=null, rfNumber=[20], rfOrder=20, authorNames=YING Q, WU G, journalName=Ren Fail, refType=null, unstructuredReference=YING Q, WU G. Molecular mechanisms involved in podocyte EMT and concomitant diabetic kidney diseases: an update [J]. Ren Fail, 2017, 39（1）: 474-483., articleTitle=Molecular mechanisms involved in podocyte EMT and concomitant diabetic kidney diseases: an update, refAbstract=null), Reference(id=1241029122630144231, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2020, volume=31, issue=5, pageStart=907, pageEnd=919, url=null, language=null, rfNumber=[21], rfOrder=21, authorNames=PACKER M, journalName=J Am Soc Nephrol, refType=null, unstructuredReference=PACKER M. Role of impaired nutrient and oxygen deprivation signaling and deficient autophagic flux in diabetic CKD development: implications for understanding the effects of sodium-glucose cotransporter 2-inhibitors [J]. J Am Soc Nephrol, 2020,31（5）: 907-919., articleTitle=Role of impaired nutrient and oxygen deprivation signaling and deficient autophagic flux in diabetic CKD development: implications for understanding the effects of sodium-glucose cotransporter 2-inhibitors, refAbstract=null), Reference(id=1241029122705641706, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2021, volume=10, issue=6, pageStart=1184, pageEnd=null, url=null, language=null, rfNumber=[22], rfOrder=22, authorNames=LIN Q, BANU K, NI Z, journalName=J Clin Med, refType=null, unstructuredReference=LIN Q, BANU K, NI Z, et al. Podocyte autophagy in homeostasis and disease [J]. J Clin Med, 2021, 10（6）: 1184., articleTitle=Podocyte autophagy in homeostasis and disease, refAbstract=null), Reference(id=1241029122785333487, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=30, issue=7, pageStart=554, pageEnd=557, url=null, language=null, rfNumber=[23], rfOrder=23, authorNames=熊哲学, 李凝旭, 唐明娟, journalName=中国糖尿病学杂志, refType=null, unstructuredReference=熊哲学, 李凝旭, 唐明娟. 钠-葡萄糖协同转运蛋白2抑制剂对足细胞自噬影响及其肾脏保护机制的研究进展[J]. 中国糖尿病学杂志, 2022, 30（7）: 554-557., articleTitle=钠-葡萄糖协同转运蛋白2抑制剂对足细胞自噬影响及其肾脏保护机制的研究进展, refAbstract=null), Reference(id=1241029122877608180, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=30, issue=7, pageStart=554, pageEnd=557, url=null, language=null, rfNumber=[23], rfOrder=24, authorNames=XIONG ZX, LI NX, TANG MJ, journalName=Chin J Diabetes, refType=null, unstructuredReference=XIONG ZX, LI NX, TANG MJ. Research progress on the effect of SGLT2 inhibitor to podocyte autophagy and its renal protective mechanism [J]. Chin J Diabetes, 2022, 30（7）: 554-557., articleTitle=Research progress on the effect of SGLT2 inhibitor to podocyte autophagy and its renal protective mechanism, refAbstract=null), Reference(id=1241029123011825912, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=13, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[24], rfOrder=25, authorNames=LV X, WANG J, ZHANG L, journalName=Front Immunol, refType=null, unstructuredReference=LV X, WANG J, ZHANG L, et al. Canagliflozin reverses Th1/Th2 imbalance and promotes podocyte autophagy in rats with membranous nephropathy [J]. Front Immunol, 2022, 13 : 993869., articleTitle=Canagliflozin reverses Th1/Th2 imbalance and promotes podocyte autophagy in rats with membranous nephropathy, refAbstract=null), Reference(id=1241029123120877821, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2023, volume=13, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[25], rfOrder=26, authorNames=YANG Y, LI Q, LING Y, journalName=Front Immunol, refType=null, unstructuredReference=YANG Y, LI Q, LING Y, et al. m6A eraser FTO modulates autophagy by targeting SQSTM1/P62 in the prevention of canagliflozin against renal fibrosis [J]. Front Immunol, 2023, 13 : 1094556., articleTitle=m6A eraser FTO modulates autophagy by targeting SQSTM1/P62 in the prevention of canagliflozin against renal fibrosis, refAbstract=null), Reference(id=1241029123246706943, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2021, volume=40, issue=5, pageStart=369, pageEnd=377, url=null, language=null, rfNumber=[26], rfOrder=27, authorNames=STEWART T, ZEA A, AVILES D, journalName=Fetal Pediatr Pathol, refType=null, unstructuredReference=STEWART T, ZEA A, AVILES D. Expression of the IL-2R in human podocytes and the effect of activation on autophagy and apoptosis [J]. Fetal Pediatr Pathol, 2021, 40（5）: 369-377., articleTitle=Expression of the IL-2R in human podocytes and the effect of activation on autophagy and apoptosis, refAbstract=null), Reference(id=1241029123359953157, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2021, volume=12, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[27], rfOrder=28, authorNames=NAKAGAWA T, SANCHEZ-LOZADA LG, ANDRES-HERNANDO A, journalName=Front Immunol, refType=null, unstructuredReference=NAKAGAWA T, SANCHEZ-LOZADA LG, ANDRES-HERNANDO A, et al. Endogenous fructose metabolism could explain the Warburg effect and the protection of SGLT2 inhibitors in chronic kidney disease[J]. Front Immunol, 2021, 12 : 694457., articleTitle=Endogenous fructose metabolism could explain the Warburg effect and the protection of SGLT2 inhibitors in chronic kidney disease, refAbstract=null), Reference(id=1241029123448033546, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=24, issue=10, pageStart=1950, pageEnd=1956, url=null, language=null, rfNumber=[28], rfOrder=29, authorNames=SEN T, KOSHINO A, NEAL B, journalName=Diabetes Obes Metab, refType=null, unstructuredReference=SEN T, KOSHINO A, NEAL B, et al. Mechanisms of action of the sodium-glucose cotransporter-2 （SGLT2） inhibitor canagliflozin on tubular inflammation and damage: a post hoc mediation analysis of the CANVAS trial [J]. Diabetes Obes Metab, 2022, 24（10）:1950-1956., articleTitle=Mechanisms of action of the sodium-glucose cotransporter-2 （SGLT2） inhibitor canagliflozin on tubular inflammation and damage: a post hoc mediation analysis of the CANVAS trial, refAbstract=null), Reference(id=1241029123536113934, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2019, volume=95, issue=4, pageStart=830, pageEnd=845, url=null, language=null, rfNumber=[29], rfOrder=30, authorNames=ZHOU L, CHEN X, LU M, journalName=Kidney Int, refType=null, unstructuredReference=ZHOU L, CHEN X, LU M, et al. Wnt/β-catenin links oxidative stress to podocyte injury and proteinuria [J]. Kidney Int, 2019, 95（4）: 830-845., articleTitle=Wnt/β-catenin links oxidative stress to podocyte injury and proteinuria, refAbstract=null), Reference(id=1241029123636777235, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2021, volume=117, issue=1, pageStart=74, pageEnd=84, url=null, language=null, rfNumber=[30], rfOrder=31, authorNames=PACKER M, journalName=Cardiovasc Res, refType=null, unstructuredReference=PACKER M. Critical examination of mechanisms underlying the reduction in heart failure events with SGLT2 inhibitors:identification of a molecular link between their actions to stimulate erythrocytosis and to alleviate cellular stress [J]. Cardiovasc Res,2021, 117（1）: 74-84., articleTitle=Critical examination of mechanisms underlying the reduction in heart failure events with SGLT2 inhibitors:identification of a molecular link between their actions to stimulate erythrocytosis and to alleviate cellular stress, refAbstract=null), Reference(id=1241029123716469015, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2019, volume=20, issue=15, pageStart=3711, pageEnd=null, url=null, language=null, rfNumber=[31], rfOrder=32, authorNames=DUNI A, LIAKOPOULOS V, ROUMELIOTIS S, journalName=Int J Mol Sci, refType=null, unstructuredReference=DUNI A, LIAKOPOULOS V, ROUMELIOTIS S, et al. Oxidative stress in the pathogenesis and evolution of chronic kidney disease:untangling Ariadne’s thread [J]. Int J Mol Sci, 2019, 20（15） :3711., articleTitle=Oxidative stress in the pathogenesis and evolution of chronic kidney disease:untangling Ariadne’s thread, refAbstract=null), Reference(id=1241029123821326622, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2018, volume=8, issue=1, pageStart=4029, pageEnd=null, url=null, language=null, rfNumber=[32], rfOrder=33, authorNames=KAMEZAKI M, KUSABA T, KOMAKI K, journalName=Sci Rep, refType=null, unstructuredReference=KAMEZAKI M, KUSABA T, KOMAKI K, et al. Comprehensive renoprotective effects of ipragliflozin on early diabetic nephropathy in mice [J]. Sci Rep, 2018, 8（1）: 4029., articleTitle=Comprehensive renoprotective effects of ipragliflozin on early diabetic nephropathy in mice, refAbstract=null), Reference(id=1241029123901018401, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=163, issue=1, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[33], rfOrder=34, authorNames=AUDZEYENKA I, BIERZYNSKA A, LAY AC, journalName=Endocrinology, refType=null, unstructuredReference=AUDZEYENKA I, BIERZYNSKA A, LAY AC. Podocyte bioenergetics in the development of diabetic nephropathy: the role of mitochondria [J]. Endocrinology, 2022, 163（1）: bqab234., articleTitle=Podocyte bioenergetics in the development of diabetic nephropathy: the role of mitochondria, refAbstract=null), Reference(id=1241029124001681699, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=8, issue=2, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[34], rfOrder=35, authorNames=MIMA A, journalName=Heliyon, refType=null, unstructuredReference=MIMA A. Mitochondria-targeted drugs for diabetic kidney disease[J]. Heliyon, 2022, 8（2）: e08878., articleTitle=Mitochondria-targeted drugs for diabetic kidney disease, refAbstract=null), Reference(id=1241029124072984871, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2021, volume=162, issue=8, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[35], rfOrder=36, authorNames=HOONG CWS, CHUA MWJ, journalName=Endocrinology, refType=null, unstructuredReference=HOONG CWS, CHUA MWJ. SGLT2 inhibitors as calorie restriction mimetics: insights on longevity pathways and age-related diseases[J]. Endocrinology, 2021, 162（8）: bqab079., articleTitle=SGLT2 inhibitors as calorie restriction mimetics: insights on longevity pathways and age-related diseases, refAbstract=null), Reference(id=1241029124144288041, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2021, volume=7, issue=6, pageStart=438, pageEnd=451, url=null, language=null, rfNumber=[36], rfOrder=37, authorNames=SUN Y, CUI S, HOU Y, journalName=Kidney Dis （Basel）, refType=null, unstructuredReference=SUN Y, CUI S, HOU Y, et al. The updates of podocyte lipid metabolism in proteinuric kidney disease [J]. Kidney Dis （Basel）,2021, 7（6）: 438-451., articleTitle=The updates of podocyte lipid metabolism in proteinuric kidney disease, refAbstract=null), Reference(id=1241029124249145644, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2017, volume=292, issue=13, pageStart=5335, pageEnd=5348, url=null, language=null, rfNumber=[37], rfOrder=38, authorNames=WANG XX, LEVI J, LUO Y, journalName=J Biol Chem, refType=null, unstructuredReference=WANG XX, LEVI J, LUO Y, et al. SGLT2 protein expression is increased in human diabetic nephropathy: SGLT2 protein inhibition decreases renal lipid accumulation, inflammation, and the development of nephropathy in diabetic mice [J]. J Biol Chem,2017, 292（13）: 5335-5348., articleTitle=SGLT2 protein expression is increased in human diabetic nephropathy: SGLT2 protein inhibition decreases renal lipid accumulation, inflammation, and the development of nephropathy in diabetic mice, refAbstract=null), Reference(id=1241029124333031729, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2023, volume=13, issue=1, pageStart=2026, pageEnd=null, url=null, language=null, rfNumber=[38], rfOrder=39, authorNames=JO HA, SEO JH, LEE S, journalName=Sci Rep, refType=null, unstructuredReference=JO HA, SEO JH, LEE S, et al. Metabolomic profiling in kidney cells treated with a sodium glucose-cotransporter 2 inhibitor [J]. Sci Rep, 2023, 13（1）: 2026., articleTitle=Metabolomic profiling in kidney cells treated with a sodium glucose-cotransporter 2 inhibitor, refAbstract=null), Reference(id=1241029124421112118, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2023, volume=12, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[39], rfOrder=40, authorNames=GE M, MOLINA J, KIM JJ, journalName=Elife, refType=null, unstructuredReference=GE M, MOLINA J, KIM JJ, et al. Empagliflozin reduces podocyte lipotoxicity in experimental Alport syndrome [J]. Elife, 2023, 12:e83353., articleTitle=Empagliflozin reduces podocyte lipotoxicity in experimental Alport syndrome, refAbstract=null), Reference(id=1241029124525969721, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2022, volume=14, issue=4, pageStart=236, pageEnd=246, url=null, language=null, rfNumber=[40], rfOrder=41, authorNames=DURCAN E, OZKAN S, SAYGI HI, journalName=J Diabetes, refType=null, unstructuredReference=DURCAN E, OZKAN S, SAYGI HI, et al. Effects of SGLT2 inhibitors on patients with diabetic kidney disease: a preliminary study on the basis of podocyturia [J]. J Diabetes, 2022, 14（4）:236-246., articleTitle=Effects of SGLT2 inhibitors on patients with diabetic kidney disease: a preliminary study on the basis of podocyturia, refAbstract=null), Reference(id=1241029124605661499, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, doi=null, pmid=null, pmcid=null, year=2021, volume=10, issue=7, pageStart=1815, pageEnd=null, url=null, language=null, rfNumber=[41], rfOrder=42, authorNames=BOECKHAUS J, GROSS O, BOECKHAUS J, journalName=Cells, refType=null, unstructuredReference=BOECKHAUS J, GROSS O, BOECKHAUS J, et al. Sodium-glucose cotransporter-2 inhibitors in patients with hereditary podocytopathies, Alport syndrome, and FSGS: a case series to better plan a large-scale study [J]. Cells, 2021, 10（7）: 1815., articleTitle=Sodium-glucose cotransporter-2 inhibitors in patients with hereditary podocytopathies, Alport syndrome, and FSGS: a case series to better plan a large-scale study, refAbstract=null)], funds=[Fund(id=1241029118842687588, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, awardId=2023Y0973, language=CN, fundingSource=2023年度云南省教育厅科学研究基金研究生项目(2023Y0973), fundOrder=null, country=null), Fund(id=1241029118930767982, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, awardId=2022KBG059, language=CN, fundingSource=大理市2022年科技计划项目(2022KBG059), fundOrder=null, country=null), Fund(id=1241029119010459763, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, awardId=DFYJC-202108, language=CN, fundingSource=大理大学第一附属医院杰出中青年人才项目(DFYJC-202108), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1241029115239781367, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, xref=1., ext=[AuthorCompanyExt(id=1241029115252364280, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115239781367, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Clinical Medical College of Dali University, Dali YUNNAN 671003, China), AuthorCompanyExt(id=1241029115260752889, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115239781367, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.大理大学临床医学院，云南 大理　671003)]), AuthorCompany(id=1241029115315278842, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, xref=2., ext=[AuthorCompanyExt(id=1241029115319473147, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115315278842, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.Department of Nephrology, the First Affiliated Hospital of Dali University, Dali YUNNAN 671013, China), AuthorCompanyExt(id=1241029115327861756, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115315278842, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.大理大学第一附属医院 肾脏内科，云南 大理　671013)]), AuthorCompany(id=1241029115386582013, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, xref=3., ext=[AuthorCompanyExt(id=1241029115390776318, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115386582013, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.Department of Human Anatomy, Basic Medical College of Dali University, Dali YUNNAN 671003, China), AuthorCompanyExt(id=1241029115399164927, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241022579528487756, companyId=1241029115386582013, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.大理大学基础医学院 解剖教研室，云南 大理　671003)])], figs=null, attaches=null, journal=Journal(id=1205114437246812164, delFlag=0, nameCn=中国新药与临床杂志, nameEn=Chinese Journal of New Drugs and Clinical Remedies, nameHistory1=null, nameHistory2=null, issn=1007-7669, eissn=, cn=31-1746/R, coden=null, periodic=月刊, language=CN, oaType=1, 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=, officePhone=, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=4CRZH/cEJmlFWJuWhAUDig==, journalPrice=null, startedYear=null, abbrevIsoEn=Chinese Journal of New Drugs and Clinical Remedies, journalRemark=null, publicationField=null, createdTime=1765251271787, updatedTime=1765252216403, createdBy=18614031015, updatedBy=13701087609, firstLetterCn=C, firstLetterEn=C, subjectCode=Life Sciences, subjectName=生命医学, subjectCodeEn=Life Sciences, subjectNameEn=null, picCn=4CRZH/cEJmlFWJuWhAUDig==, picEn=N3vp8/tZorUwVBJknBXdng==, jcr=null, cjcr=null, exts=[JournalExt(id=1205118399413203150, language=CN, name=中国新药与临床杂志, 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=1765252216437, updatedTime=1765252216437, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=http://xyyl.cbpt.cnki.net/index.aspx?t=1, submissionEditorUrl=http://xyyl.cbpt.cnki.net/index.aspx?t=3, submissionReviewUrl=http://xyyl.cbpt.cnki.net/index.aspx?t=2, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1205118399467729103, language=EN, name=Chinese Journal of New Drugs and Clinical Remedies, 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=1765252216450, updatedTime=1765252216450, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=http://xyyl.cbpt.cnki.net/index.aspx?t=1, submissionEditorUrl=http://xyyl.cbpt.cnki.net/index.aspx?t=3, submissionReviewUrl=http://xyyl.cbpt.cnki.net/index.aspx?t=2, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1205117082300743687, websiteList=[Website(id=1205118568049389783, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1205117082300743687, 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/zgxyylczz/CN, language=CN, createTime=1765252256643, createBy=18614031015, updateTime=1765252598399, updateBy=18614031015, name=中国新药与临床杂志-中文, tplId=1146099689490845704, title=中国新药与临床杂志, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1205154564317098673, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568049389783, code=articleTextType, value=kx, createTime=1765260838822, updateTime=1765260838822, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154564300321454, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568049389783, code=banner, value=null, createTime=1765260838818, updateTime=1765260838818, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154564333875892, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568049389783, code=grayFlag, value=0, createTime=1765260838826, updateTime=1765260838826, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154564296127149, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568049389783, code=logo, value=https://castjournals.cast.org.cn/joweb/zgxyylczz/CN/file/pic?fileId=EPNvNLzzPrR2hCakA9eyOQ==, createTime=1765260838817, updateTime=1765260838817, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154564354847414, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568049389783, code=minRunFlag, value=0, createTime=1765260838831, updateTime=1765260838831, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154564312904368, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568049389783, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/zgxyylczz/CN/file/pic, createTime=1765260838821, updateTime=1765260838821, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154564342264501, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568049389783, code=silenceFlag, value=0, createTime=1765260838828, updateTime=1765260838828, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154564308710063, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568049389783, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1765260838820, updateTime=1765260838820, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154564325487282, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568049389783, code=themeColor, value=null, createTime=1765260838824, updateTime=1765260838824, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154564329681587, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568049389783, code=themeStyle, value=null, createTime=1765260838825, updateTime=1765260838825, creator=18614031015, updator=18614031015)]), Website(id=1205118568124887278, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1205117082300743687, 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/zgxyylczz/EN, language=EN, createTime=1765252256661, createBy=18614031015, updateTime=1765252618802, updateBy=18614031015, name=中国新药与临床杂志-英文, tplId=1146101810881728533, title=Chinese Journal of New Drugs and Clinical Remedies, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1205154594314756492, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887278, code=articleTextType, value=kx, createTime=1765260845974, updateTime=1765260845974, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154594297979273, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887278, code=banner, value=null, createTime=1765260845970, updateTime=1765260845970, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154594331533711, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887278, code=grayFlag, value=0, createTime=1765260845978, updateTime=1765260845978, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154594289590664, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887278, code=logo, value=https://castjournals.cast.org.cn/joweb/zgxyylczz/EN/file/pic?fileId=EPNvNLzzPrR2hCakA9eyOQ==, createTime=1765260845968, updateTime=1765260845968, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154594344116625, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887278, code=minRunFlag, value=0, createTime=1765260845981, updateTime=1765260845981, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154594310562187, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887278, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/zgxyylczz/EN/file/pic, createTime=1765260845973, updateTime=1765260845973, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154594335728016, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887278, code=silenceFlag, value=0, createTime=1765260845979, updateTime=1765260845979, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154594302173578, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887278, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1765260845971, updateTime=1765260845971, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154594323145101, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887278, code=themeColor, value=null, createTime=1765260845976, updateTime=1765260845976, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154594327339406, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887278, code=themeStyle, value=null, createTime=1765260845977, updateTime=1765260845977, creator=18614031015, updator=18614031015)])], journalTitle=中国新药与临床杂志, weixinUrl=null, journalUrl=null, iacademicId=null, status=1, seqNo=null, journalTitleEn=Chinese Journal of New Drugs and Clinical Remedies, journalPhotoCn=4CRZH/cEJmlFWJuWhAUDig==, journalPhotoEn=N3vp8/tZorUwVBJknBXdng==, journalFirstLetter=C, 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), detailUrlCn=https://castjournals.cast.org.cn/joweb/zgxyylczz/CN/10.14109/j.cnki.xyylc.2024.09.02, detailUrlEn=https://castjournals.cast.org.cn/joweb/zgxyylczz/EN/10.14109/j.cnki.xyylc.2024.09.02, pdfUrlCn=https://castjournals.cast.org.cn/joweb/zgxyylczz/CN/PDF/10.14109/j.cnki.xyylc.2024.09.02, pdfUrlEn=https://castjournals.cast.org.cn/joweb/zgxyylczz/EN/PDF/10.14109/j.cnki.xyylc.2024.09.02, aliStartDate=null, aliEndDate=null, collectionFlag=false, citedCount=null, citedUrl=null, reference=null)
收藏切换
钠-葡萄糖共转运蛋白2抑制剂抗足细胞损伤机制研究进展
收藏切换
PDF下载
环薇 1 , 李潇 2 , 洪文娟 2 , 罗晓菲 1 , 成家茂 3
中国新药与临床杂志 | 综述 2024,43(9): 646-650
收起
收藏切换
中国新药与临床杂志 | 综述 2024, 43(9): 646-650
钠-葡萄糖共转运蛋白2抑制剂抗足细胞损伤机制研究进展
全屏
环薇1 , 李潇2 , 洪文娟2, 罗晓菲1, 成家茂3
作者信息
  • 1.大理大学临床医学院，云南 大理　671003
  • 2.大理大学第一附属医院 肾脏内科，云南 大理　671013
  • 3.大理大学基础医学院 解剖教研室，云南 大理　671003

    • 环薇，女，硕士在读，主要从事肾脏疾病的研究，E-mail：

通讯作者:

李潇，E-mail：
成家茂，E-mail：
Research progress on mechanism of sodium-glucose cotransporter 2 inhibitors against podocyte damage
Wei HUAN1 , Xiao LI2 , Wen-juan HONG2, Xiao-fei LUO1, Jia-mao CHENG3
Affiliations
  • 1.Clinical Medical College of Dali University, Dali YUNNAN 671003, China
  • 2.Department of Nephrology, the First Affiliated Hospital of Dali University, Dali YUNNAN 671013, China
  • 3.Department of Human Anatomy, Basic Medical College of Dali University, Dali YUNNAN 671003, China
出版时间: 2024-09-25 doi: 10.14109/j.cnki.xyylc.2024.09.02
文章导航
收藏切换
摘要
收起

慢性肾脏病是一个全球性的公共卫生问题，可进展为终末期肾脏病。足细胞损伤是多种肾小球疾病常见的病理类型，蛋白尿的发生可随足细胞数量的减少而增加。足细胞损伤的治疗仍受到病因复杂、免疫治疗副作用大、非免疫抑制靶向治疗起步晚等诸多限制。近年来，关于钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）在慢性肾脏病中的作用机制研究越来越广泛而深入，但以足细胞为靶点的研究报道仍较少。本文综述SGLT2i抗足细胞损伤机制，以期为SGLT2i在治疗足细胞损伤相关性疾病中的应用提供更充分的理论支持。

钠-葡萄糖共转运蛋白2抑制剂  /  肾功能衰竭  /  足细胞  /  慢性肾脏病

Chronic kidney disease is a global public health problem, which can progress to end-stage kidney disease. Podocyte injury is a common pathological type of various glomerular diseases, and the incidence of proteinuria can increase with the decrease of podocyte number. The treatment of podocyte injury is still limited by complex etiology, significant side effects of immunotherapy, and late initiation of targeted non-immunosuppressive therapy. In recent years, the research on the mechanism of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in chronic kidney disease had become increasingly extensive and in-depth, but there were still few reports on targeting podocytes. In this paper, the mechanism of SGLT2i against podocyte injury is reviewed, which provides a more sufficient theoretical foundation for the application of SGLT2i in the treatment of podocyte injury-related diseases.

sodium-glucose cotransporter 2 inhibitors  /  kidney failure  /  podocytes  /  chronic kidney disease
环薇, 李潇, 洪文娟, 罗晓菲, 成家茂. 钠-葡萄糖共转运蛋白2抑制剂抗足细胞损伤机制研究进展. 中国新药与临床杂志, 2024 , 43 (9) : 646 -650 . DOI: 10.14109/j.cnki.xyylc.2024.09.02
Wei HUAN, Xiao LI, Wen-juan HONG, Xiao-fei LUO, Jia-mao CHENG. Research progress on mechanism of sodium-glucose cotransporter 2 inhibitors against podocyte damage[J]. Chinese Journal of New Drugs and Clinical Remedies, 2024 , 43 (9) : 646 -650 . DOI: 10.14109/j.cnki.xyylc.2024.09.02
正文
收起
慢性肾脏病（chronic kidney disease, CKD）是各种原因导致的肾脏结构和功能的持续性改变，可逐渐进展为终末期肾脏病（end-stage renal disease, ESRD）[1]。足细胞覆盖于肾小球毛细血管外侧，在肾小球滤过方面起重要作用，其功能和结构的损伤与CKD的进展及ESRD密切相关[2]。钠-葡萄糖共转运蛋白2（sodium-glucose cotransporter 2, SGLT2）在近端肾小管上皮细胞中分布，SGLT2抑制剂（SGLT2i）作为一种新型降血糖药，能延缓CKD的进展并降低患者死亡率[3]。越来越多的研究证明SGLT2i可能对除近端肾小管上皮细胞以外的细胞发挥作用，如肾小球内皮细胞、系膜细胞和足细胞[4]。此外，SGLT2在蛋白尿性肾病动物模型及体外培养的足细胞中均有表达，故可作为SGLT2i的靶标[5]。尽管缺乏足细胞受益于SGLT2i的直接证据，但较多的研究表明SGLT2i对足细胞具有保护作用。本文主要就SGLT2i修复足细胞损伤的机制进行综述。
足细胞的结构和功能
收起
足细胞、毛细血管上皮细胞和肾小球基底膜共同组成肾小球滤过膜屏障，足细胞表面的顶端结构带负电荷，能限制阴离子电荷通过。电镜下可观察到足细胞从胞体伸出几个大的初级突起，后者又分出许多指状次级突起即足突（foot process, FP），相邻的FP通过狭缝隔膜（slit diaphragm，SD）的特定蛋白质连接附着在肾小球上，形成滤过屏障[6]。FP融合、消失等形态学改变是肾小球疾病的共同特征。FP及SD是防止蛋白质丢失的最后屏障，故蛋白尿为足细胞损伤的主要临床表现。足细胞是终末分化的上皮细胞，当足细胞丢失时，其祖细胞可分化新的足细胞，但再生效率低下[7]。随着足细胞损伤的扩大，其他足细胞会出现继发性损伤，最终导致ESRD[8]。临床上治疗足细胞损伤引起蛋白尿的药物有激素、免疫抑制剂、肾素-血管紧张素-醛固酮系统（RAAS）抑制剂等，但均有一定的临床使用局限性，SGLT2i为治疗足细胞损伤提供了新的用药思路。
SGLT2i的肾脏保护作用及其对足细胞的影响
收起
1　肾脏保护作用
近年来研究发现，无论是否合并糖尿病，SGLT2i均能改善患者的肾脏和心血管结局[9]。肾小球疾病所致的肾单位损失可引起残余肾单位代偿性出现肾小球内压增加、肾小球肥大和高滤过，并使残余肾单位的肾小球进一步损伤，而降低肾小球内压一直被认为是保持CKD残余肾单位功能的可行策略[4]。通过抑制管球反馈来降低肾小球内压和高滤过是SGLT2i延缓CKD进展的主要机制[9]。SGLT2i还具有延缓肾小球滤过率下降、逆转蛋白尿进展、改善肾小管氧合和代谢、减轻肾脏炎症和纤维化等肾脏保护作用[10]。尽管SGLT2i参与了改善糖尿病肾病的各个病理方面，但与SGLT2相关的足细胞损伤机制仍未完全阐明[11]，SGLT2i抗足细胞损伤机制目前也尚不十分清楚。
2　对足细胞的影响
SGLT2i在糖尿病肾病中具有维持足细胞完整性、改善SD功能障碍、恢复足细胞上皮-间质转化（EMT）、抑制足细胞凋亡、增强足细胞自噬、防止足细胞丢失等保护作用[12]。由于足细胞表达SGLT2蛋白，因此使用达格列净能限制蛋白尿性肾病模型小鼠足细胞的损伤和丢失[5]。在一项动物实验研究中，使用恩格列净干预的糖尿病肾病合并肥胖型BTBR ob/ob小鼠与未接受治疗干预的BTBR ob/ob小鼠以及野生型BTBR WT小鼠进行对照，对足细胞进行计数，并测量足细胞足突的长度。结果表明，经恩格列净治疗后的BRBT ob/ob小鼠足细胞数量与正常对照组一致，虽然不能还原已经丢失了的足细胞，但能通过改善足细胞FP的消失及调节FP的长度来修复受损的足细胞[13]。此外，使用达格列净或恩格列净可改善高糖毒性导致的足细胞功能障碍和消失[14]。笔者由此推测，在足细胞脱落前，通过SGLT2i治疗可恢复糖尿病肾病患者受损的足细胞，但在不合并糖尿病的CKD中仍缺乏用药依据，且具体机制尚不清楚。
SGLT2i抗足细胞损伤的机制
收起
1　抑制足细胞凋亡
转化生长因子（TGF）-β1是一种纤维化细胞因子，能激活p38MAPK、Smad7、Notch途径以及增加SGLT2的基因表达，从而诱发蛋白尿、促进肾小球硬化及足细胞凋亡[15]。达格列净能显著降低TGF-β1表达，恩格列净能下调SGLT2及抑制TGF-β/Smad信号通路相关蛋白表达，减少肾单位丢失及抑制足细胞凋亡[15]；还能显著抑制高糖诱导的足细胞中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和TGF-β mRNA表达，从而抑制足细胞凋亡[16]。研究证明，SGLT2i可以抑制高糖环境下PI3K/AKT、WNT/β-catenin、JAK/STAT3等通路激活所导致的足细胞凋亡，但SGLT2i也可通过增强STAT3 mRNA表达来促进细胞凋亡[12]。因此，足细胞凋亡能影响CKD的进展，其机制与糖脂毒性、氧化应激、炎症损伤及自噬减弱等方面有关。
2　稳定足细胞肌动蛋白骨架（F-actin）结构
F-actin广泛分布于FP中，FP顶端有Podocalyxin穿膜蛋白，FP基底侧有抗肌萎缩蛋白聚糖（dystroglycan）、整合素α3β1、跨膜蛋白CD151，SD周围有nephrin、podocin、P-cadherin、JAM4蛋白等。F-actin相关蛋白对维持足细胞正常功能起着至关重要的作用，一旦F-actin的结构发生改变，将会发生不可逆转的蛋白尿[17]。Nephrin下调可能导致FP消失和SD破裂，恩格列净可以通过增强nephrin的表达来减少蛋白尿，改善足细胞FP的消失[18]。白蛋白超负荷引起肾小球滤过功能障碍，导致F-actin重组，使用达格列净可稳定F-actin并改善足细胞丢失和功能失调，从而减少蛋白尿和减轻肾小球损伤[13]。因此，SGLT2i可能通过重塑F-actin结构来改善足细胞损伤及其功能障碍。
3　抑制足细胞EMT
足细胞发生EMT是多种CKD患者蛋白尿及疾病进展的重要机制。EMT发生时F-actin重新排列，滤过屏障发生改变，最终导致肾纤维化[19]。高糖环境下，TGF-β/Smad、WNT/β-catenin、Integrins/ILK、MAPKs、PI3K/AKT/mTOR、Jagged/Notch和NF-κB等信号通路激活，参与足细胞的EMT[20]。达格列净可以通过下调IGF1R/PI3K通路来抑制糖尿病状态下的足细胞EMT，从而减轻肾纤维化[11]。
4　增强足细胞自噬
高水平自噬是足细胞维持其结构和功能完整性的一种自我调控过程，也是足细胞损伤的关键因素。在营养剥夺和缺氧状态下，AMPK、SIRT1、缺氧诱导因子（HIF）-1α和HIF-2α可以通过促进自噬通量来发挥肾脏保护作用[21]。AMPK是诱导自噬的重要底物，也是多种营养和代谢途径的关键调节因子，可通过抑制mTOR或直接磷酸化ULK1来调节自噬[22]。在营养缺乏状态下，SGLT2i能激活mTOR/AMPK/SIRT1通路增强足细胞自噬，使肾脏获益[23]。卡格列净能通过下调mTOR/ULK1信号通路来改善足细胞自噬，减轻足细胞损伤[24]，还可通过调节肾小管STAT1/PPARα/FAO轴改善自噬[25]。此外，达格列净上调了Beclin-1和LC3 Ⅱ/LC3 Ⅰ的表达，促进足细胞自噬体周转和自噬溶酶体降解[15]。因此，SGLT2i可能通过调节足细胞自噬失衡状态使CKD患者获益。
5　控制炎症反应
慢性低度炎症是CKD的发病基础。足细胞中表达炎症介质并产生促炎因子，当炎症受体激活时足细胞凋亡增加，导致蛋白尿进展[26]。SGLT2i具有强大的改善代谢和抗炎作用，通过阻断近端小管对葡萄糖的重吸收，减少葡萄糖转化为果糖的量，控制炎症反应使肾脏获益[27]。卡格列净还可通过直接促进尿中炎性标志物排泄和降低尿蛋白，间接减轻肾小管炎症，改善足细胞功能障碍和丧失[28]。因此，控制炎症反应是减轻足细胞损伤的有效手段。
6　减轻氧化应激
足细胞是代谢非常活跃的细胞，容易受到氧化应激的影响。氧化应激在CKD的进展中起关键作用，且与足细胞损伤和蛋白尿的发展有关。研究表明WNT/β-catenin信号通路参与了氧化应激过程并引起足细胞功能障碍[29]。SGLT2i可通过激活SIRT1增强自噬从而减少氧化应激[30]。缺氧时肾脏深层皮质和外髓质中的氧气压力较低，HIF-1和HIF-2被激活，促红细胞生成素合成增多，氧合作用得到改善，从而促进氧气输送到心脏和其他器官，缺氧时使用SGLT2i具有相同的效果[30]。活性氧（ROS）是线粒体氧化磷酸化不可避免的产物，足细胞中ROS的产生可直接介导肾小球损伤[31]。高剂量伊格列净能减少ROS的生产，减轻足细胞的氧化应激，发挥肾保护作用[32]。
7　调节线粒体的动力学稳态
线粒体在维持足细胞稳态和足细胞病的发展中具有关键作用，因足细胞复杂的F-actin需要足够的线粒体数量及其正常功能来满足巨大的能量需求[33]。SGLT2i可通过改善线粒体动力学来提供肾脏保护[34]。卡路里限制能通过上调AMPK/SIRT1/PGC-1α信号通路来增强线粒体生物发生，改善线粒体质量，增加线粒体DNA（mtDNA），这与SGLT2i作用一致[35]。但目前未有SGLT2i作用于足细胞线粒体的相关报道。
8　调节脂质代谢
足细胞中的SD实际上是一种脂筏结构，其胆固醇含量是其他质膜部分的5~8倍，这表明脂质代谢紊乱可能在足细胞损伤以及蛋白尿发生与发展中发挥重要作用[36]。SGLT2i通过抑制硬脂酰辅酶A去饱和酶-1（Scd-1）和二酰基甘油O-酰基转移酶1（Dgat1）基因合成，从而防止中性脂质在肾脏积累[37]。在糖尿病模型研究中，足细胞中的二酰基磷脂酰胆碱（PCaa）水平下调，而达格列净治疗后，PCaa水平显著增高，这表明达格列净可以促进足细胞的脂质代谢，维持足细胞的正常功能[38]。此外，Alport综合征患者足细胞中的胆固醇和甘油三酯水平增加，恩格列净通过将足细胞中的能量底物从葡萄糖转换成脂肪酸，从而降低足细胞中脂滴的积累，减轻肾脏脂毒性[39]。上述研究表明SGLT2i可能通过调节足细胞的脂质代谢，防止脂质累积，从而发挥肾脏保护作用。
9　其他
蛋白尿患者的尿液中可发现足细胞，且尿液中足细胞的排泄水平随着肾小球损伤的严重程度增加，SGLT2i治疗6个月后糖尿病患者尿中足细胞的排泄显著减少[40]。在一项包括局灶节段性肾小球硬化和Alport综合征在内的遗传性足细胞病的临床研究中发现，SGLT2i具有纠正RAAS抑制剂引起的血流动力学超负荷的巨大潜力[41]。因此，SGLT2i还可能通过减轻严重肾小球损伤所致的足细胞尿，改善足细胞病的肾小球血流动力学过度负荷，发挥肾保护作用。
结语
收起
早期干预或防治足细胞相关疾病，防止足细胞持续或严重损伤并进展为ESRD，减少CKD的死亡率，有针对性地研究SGLT2i的作用机制并开发药物，是近年来关注和研究的重点。本文从足细胞自身的形态结构、物质能量代谢、细胞转化、排泄及其所处微环境的炎症、氧化应激和血流动力学改变等角度，对SGLT2i的作用机制进行了初步探讨。尽管SGLT2i在实验研究和临床实践中显示出了确切而广泛的肾脏获益，但基于足细胞的获益机制研究才刚刚起步，仍需要更多的研究来更好地阐明SGLT2i对足细胞保护的作用机制。
基金
收起
  • 2023年度云南省教育厅科学研究基金研究生项目(2023Y0973)
  • 大理市2022年科技计划项目(2022KBG059)
  • 大理大学第一附属医院杰出中青年人才项目(DFYJC-202108)
文献
收起
参考文献 引证文献
排序方式：
[1]
上海市肾内科临床质量控制中心专家组. 慢性肾脏病早期筛查、诊断及防治指南（2022年版）[J]. 中华肾脏病杂志, 2022, 38（5）: 453-464.
Expert Group on Kidney Clinical Quality Control Center in Shanghai. Guidelines for early screening, diagnosis, prevention and treatment of chronic kidney disease （2022 Edition）[J]. Chin J Nephrol, 2022, 38（5）: 453-464.
[2]
LI G, KIDD J, LI PL. Podocyte lysosome dysfunction in chronic glomerular diseases [J]. Int J Mol Sci, 2020, 21（5）: 1559.
[3]
MIMA A. Sodium-glucose cotransporter2 inhibitors in patients with non-diabetic chronic kidney disease [J]. Adv Ther, 2021, 38（5）:2201-2212.
[4]
MIYATA KN, ZHANG SL, CHAN JSD. The rationale and evidence for SGLT2 inhibitors as a treatment for nondiabetic glomerular disease [J]. Glomerular Dis, 2021, 1（1）: 21-33.
[5]
CASSIS P, LOCATELLI M, CERULLO D, et al. SGLT2 inhibitor dapagliflozin limits podocyte damage in proteinuric nondiabetic nephropathy [J]. JCI Insight, 2018, 3（15）: e98720.
[6]
GARG P. A review of podocyte biology [J]. Am J Nephrol, 2018,47 Suppl 1 : 3-13.
[7]
KOPP JB, ANDERS HJ, SUSZTAK K, et al. Podocytopathies [J]. Nat Rev Dis Primers, 2020, 6（1）: 68.
[8]
OKABE M, YAMAMOTO K, MIYAZAKI Y, et al. Indirect podocyte injury manifested in a partial podocytectomy mouse model[J]. Am J Physiol Renal Physiol, 2021, 320（5）: F922-F933.
[9]
YAU K, DHARIA A, ALROWIYTI I, et al. Prescribing SGLT2 inhibitors in patients with CKD: expanding indications and practical considerations[J]. Kidney Int Rep, 2022, 7（7）: 1463-1476.
[10]
BAILEY CJ, DAY C, BELLARY S. Renal protection with SGLT2 inhibitors: effects in acute and chronic kidney disease [J]. Curr Diab Rep, 2022, 22（1）: 39-52.
[11]
GUO R, WANG P, ZHENG X, et al. SGLT2 inhibitors suppress epithelial-mesenchymal transition in podocytes under diabetic conditions via downregulating the IGF1R/PI3K pathway [J]. Front Pharmacol, 2022, 13 : 897167.
[12]
CHEN X, WANG J, LIN Y, et al. Signaling pathways of podocyte injury in diabetic kidney disease and the effect of sodium-glucose cotransporter 2 inhibitors[J]. Cells, 2022, 11（23）: 3913.
[13]
HUDKINS KL, LI X, HOLLAND AL, et al. Regression of diabetic nephropathy by treatment with empagliflozin in BTBR ob/ob mice[J]. Nephrol Dial Transplant, 2022, 37（5）: 847-859.
[14]
FONSECA-CORREA JI, CORREA-ROTTER R. Sodium-glucose cotransporter 2 inhibitors mechanisms of action: a review [J]. Front Med （Lausanne）, 2021, 8 : 777861.
[15]
TIAN Y, CHEN XM, LIANG XM, et al. SGLT2 inhibitors attenuate nephrin loss and enhance TGF-β1secretion in type 2 diabetes patients with albuminuria: a randomized clinical trial [J]. Sci Rep,2022, 12（1）: 15695.
[16]
YANG L, LIANG B, LI J, et al. Dapagliflozin alleviates advanced glycation end product induced podocyte injury through AMPK/mTOR mediated autophagy pathway[J]. Cell Signal, 2022, 90 :110206.
[17]
AHMADIAN E, EFTEKHARI A, ATAKISHIZADA S, et al. Podocytopathy: the role of actin cytoskeleton [J]. Biomed Pharmacother, 2022, 156 : 113920.
[18]
KLIMONTOV VV, KORBUT AI, TASKAEVA IS, et al. Empagliflozin alleviates podocytopathy and enhances glomerular nephrin expression indb/dbdiabetic mice[J]. World J Diabetes,2020, 11（12）: 596-610.
[19]
DAI H, LIU Q, LIU B. Research progress on mechanism of podocyte depletion in diabetic nephropathy [J]. J Diabetes Res, 2017, 2017:2615286.
[20]
YING Q, WU G. Molecular mechanisms involved in podocyte EMT and concomitant diabetic kidney diseases: an update [J]. Ren Fail, 2017, 39（1）: 474-483.
[21]
PACKER M. Role of impaired nutrient and oxygen deprivation signaling and deficient autophagic flux in diabetic CKD development: implications for understanding the effects of sodium-glucose cotransporter 2-inhibitors [J]. J Am Soc Nephrol, 2020,31（5）: 907-919.
[22]
LIN Q, BANU K, NI Z, et al. Podocyte autophagy in homeostasis and disease [J]. J Clin Med, 2021, 10（6）: 1184.
[23]
熊哲学, 李凝旭, 唐明娟. 钠-葡萄糖协同转运蛋白2抑制剂对足细胞自噬影响及其肾脏保护机制的研究进展[J]. 中国糖尿病学杂志, 2022, 30（7）: 554-557.
XIONG ZX, LI NX, TANG MJ. Research progress on the effect of SGLT2 inhibitor to podocyte autophagy and its renal protective mechanism [J]. Chin J Diabetes, 2022, 30（7）: 554-557.
[24]
LV X, WANG J, ZHANG L, et al. Canagliflozin reverses Th1/Th2 imbalance and promotes podocyte autophagy in rats with membranous nephropathy [J]. Front Immunol, 2022, 13 : 993869.
[25]
YANG Y, LI Q, LING Y, et al. m6A eraser FTO modulates autophagy by targeting SQSTM1/P62 in the prevention of canagliflozin against renal fibrosis [J]. Front Immunol, 2023, 13 : 1094556.
[26]
STEWART T, ZEA A, AVILES D. Expression of the IL-2R in human podocytes and the effect of activation on autophagy and apoptosis [J]. Fetal Pediatr Pathol, 2021, 40（5）: 369-377.
[27]
NAKAGAWA T, SANCHEZ-LOZADA LG, ANDRES-HERNANDO A, et al. Endogenous fructose metabolism could explain the Warburg effect and the protection of SGLT2 inhibitors in chronic kidney disease[J]. Front Immunol, 2021, 12 : 694457.
[28]
SEN T, KOSHINO A, NEAL B, et al. Mechanisms of action of the sodium-glucose cotransporter-2 （SGLT2） inhibitor canagliflozin on tubular inflammation and damage: a post hoc mediation analysis of the CANVAS trial [J]. Diabetes Obes Metab, 2022, 24（10）:1950-1956.
[29]
ZHOU L, CHEN X, LU M, et al. Wnt/β-catenin links oxidative stress to podocyte injury and proteinuria [J]. Kidney Int, 2019, 95（4）: 830-845.
[30]
PACKER M. Critical examination of mechanisms underlying the reduction in heart failure events with SGLT2 inhibitors:identification of a molecular link between their actions to stimulate erythrocytosis and to alleviate cellular stress [J]. Cardiovasc Res,2021, 117（1）: 74-84.
[31]
DUNI A, LIAKOPOULOS V, ROUMELIOTIS S, et al. Oxidative stress in the pathogenesis and evolution of chronic kidney disease:untangling Ariadne’s thread [J]. Int J Mol Sci, 2019, 20（15） :3711.
[32]
KAMEZAKI M, KUSABA T, KOMAKI K, et al. Comprehensive renoprotective effects of ipragliflozin on early diabetic nephropathy in mice [J]. Sci Rep, 2018, 8（1）: 4029.
[33]
AUDZEYENKA I, BIERZYNSKA A, LAY AC. Podocyte bioenergetics in the development of diabetic nephropathy: the role of mitochondria [J]. Endocrinology, 2022, 163（1）: bqab234.
[34]
MIMA A. Mitochondria-targeted drugs for diabetic kidney disease[J]. Heliyon, 2022, 8（2）: e08878.
[35]
HOONG CWS, CHUA MWJ. SGLT2 inhibitors as calorie restriction mimetics: insights on longevity pathways and age-related diseases[J]. Endocrinology, 2021, 162（8）: bqab079.
[36]
SUN Y, CUI S, HOU Y, et al. The updates of podocyte lipid metabolism in proteinuric kidney disease [J]. Kidney Dis （Basel）,2021, 7（6）: 438-451.
[37]
WANG XX, LEVI J, LUO Y, et al. SGLT2 protein expression is increased in human diabetic nephropathy: SGLT2 protein inhibition decreases renal lipid accumulation, inflammation, and the development of nephropathy in diabetic mice [J]. J Biol Chem,2017, 292（13）: 5335-5348.
[38]
JO HA, SEO JH, LEE S, et al. Metabolomic profiling in kidney cells treated with a sodium glucose-cotransporter 2 inhibitor [J]. Sci Rep, 2023, 13（1）: 2026.
[39]
GE M, MOLINA J, KIM JJ, et al. Empagliflozin reduces podocyte lipotoxicity in experimental Alport syndrome [J]. Elife, 2023, 12:e83353.
[40]
DURCAN E, OZKAN S, SAYGI HI, et al. Effects of SGLT2 inhibitors on patients with diabetic kidney disease: a preliminary study on the basis of podocyturia [J]. J Diabetes, 2022, 14（4）:236-246.
[41]
BOECKHAUS J, GROSS O, BOECKHAUS J, et al. Sodium-glucose cotransporter-2 inhibitors in patients with hereditary podocytopathies, Alport syndrome, and FSGS: a case series to better plan a large-scale study [J]. Cells, 2021, 10（7）: 1815.
2024年第43卷第9期
PDF下载
110
50
引用本文
BibTeX
文章信息
doi: 10.14109/j.cnki.xyylc.2024.09.02
  • 接收时间：2023-11-10
  • 首发时间：2026-03-18
  • 出版时间：2024-09-25
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2023-11-10
  • 录用日期：2024-08-22
基金
2023年度云南省教育厅科学研究基金研究生项目(2023Y0973)
大理市2022年科技计划项目(2022KBG059)
大理大学第一附属医院杰出中青年人才项目(DFYJC-202108)
作者信息
    1.大理大学临床医学院，云南 大理　671003
    2.大理大学第一附属医院 肾脏内科，云南 大理　671013
    3.大理大学基础医学院 解剖教研室，云南 大理　671003

通讯作者:

李潇，E-mail：
成家茂，E-mail：
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/zgxyylczz/CN/10.14109/j.cnki.xyylc.2024.09.02
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
010-62199257
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