Neferine inhibits the progression of diabetic nephropathy by modulating the miR-17-5p/nuclear factor E2-related factor 2 axis

查看全文 作　　者：HUANG [1]Hongmei;YANG [1]Maojun;LI [1]Ting;WANG [1]Dandan;LI [1]Ying;TANG [1]Xiaochi;YUAN [1]Lu;GU [1]Shi;XU [2]Yong

机构地区：[1]Department of Endocrinology,Chengdu Shuangliu District First People's Hospital(West China Airport of Sichuan University),Chengdu 610200,China;[2]Department of Endocrinology,Affiliated Hospital of Southwest Medical University,Luzhou 646000,China

出　　处：《Journal of Traditional Chinese Medicine》索引2024年第44卷第1期,共10页

基　　金：the Chengdu Health and Wellness Commission:Exploring the Mechanism of Neferine on Diabetic Nephropathy Based on mi R-17/Nrf2 Axis(No.2021127)。 摘　　要：OBJECTIVE:To investigate the effect of Neferine(Nef)on diabetic nephropathy(DN)and to explore the mechanism of Nef in DN based on miRNA regulation theory.METHODS:A DN mouse model was constructed and treated with Nef.Serum creatinine(Crea),blood urea(UREA)and urinary albumin were measured in mice by kits,and renal histopathological changes and fibrosis were observed by hematoxylin-eosin staining and Masson staining.Renal tissue superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-Px)activities were measured by enzyme-linked immunosorbent assay(ELISA).Western blotting was used to detect the expression of nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)signaling pathway-related proteins in kidney tissues.Quantitative reverse transcription-polymerase chain reaction(q RT-PCR)was used to detect the expression of miR-17-5p in kidney tissues.Subsequently,a DN in vitro model was constructed by high glucose culture of human mesangial cells(HMCs),cells were transfected with miR-17-5p mimic and/or treated with Nef,and we used q RTPCR to detect cellular miR-17 expression,flow cytometry to detect apoptosis,ELISAs to detect cellular SOD,MDA,and GSH-Px activities,Western blots to detect Nrf2/HO-1 signaling pathway-related protein expression,and dual luciferase reporter gene assays to verify the targeting relationship between Nrf2 and miR-17-5p.RESULTS:Administration of Nef significantly reduced the levels of blood glucose,Crea,and UREA and the expression of miR-17-5p,improved renal histopathology and fibrosis,significantly reduced MDA levels,elevated SOD and GSH-Px activities,and activated Nrf2 expression in kidney tissues from mice with DN.Nrf2 is a post-transcriptional target of miR-17-5p.In HMCs transfected with miR-17-5p mimics,the m RNA and protein levels of Nrf2 were significantly suppressed.Furthermore,miR-17-5p overexpression and Nef intervention resulted in a significant increase in high glucose-induced apoptosis and MDA levels in HMCs and a significant decrease in the protein expression of HO-1 and Nrf2.CONCLUSION:Collectively,these results indicate that Nef has an ameliorative effect on DN,and the mechanism may be through the miR-17-5p/Nrf2 pathway. 关键词：diabetic nephropathies NEFERINE miR-17-5p NF-E2-related factor 2 oxidative stress

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Neferine inhibits the progression of diabetic nephropathy by modulating the miR-17-5p/nuclear factor E2-related factor 2 axis

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