中药新药与临床药理2025，Vol.36Issue(12)：2044-2050,7.DOI:10.19378/j.issn.1003-9783.2025.12.004
基于HIF-1α/PINK1/Parkin通路探讨雷公藤多苷对糖尿病肾病大鼠的影响
Exploring the Effect of Tripterygium Wilfordii Multi-glycosides on Diabetic Nephropathy Rats via the HIF-1α/PINK1/Parkin Pathway
摘要
Abstract
Objective To investigate the effect of multi-glycosides of Tripterygium wilfordii(GTW)on renal injury in diabetic nephropathy(DN)rats by regulating the hypoxia-inducible factor-1α(HIF-1α)/PTEN-induced putative kinase 1(PINK1)/Parkin signaling pathway.Methods A DN rat model was established using a high-fat,high-sugar diet combined with a low-dose streptozotocin(STZ)injection.Successfully modeled rats were randomly divided into model,GTW,and valsartan(Diovan)groups,with an additional normal control group.The GTW group received GTW tablets at 6.25 mg·kg-1 by gavage,the valsartan group received valsartan at 8.33 mg·kg-1,and the normal and model groups received an equal volume of saline once daily for 6 weeks.Fasting blood glucose,24-hour urinary protein,and body mass were measured.Serum creatinine and urea nitrogen levels were detected using an automated biochemical analyzer.Renal histopathological damage was observed by HE staining.mRNA and protein expression levels of HIF-1α,PINK1,Parkin,LC3-Ⅱ,and Beclin1 were detected by qRT-PCR and Western Blot,respectively.Results Compared with the normal group,the model group showed increased mRNA and protein expression on fasting blood glucose,24-hour urinary protein,serum creatinine,urea nitrogen levels,and HIF-1α(P＜0.05),and decreased body mass and mRNA/protein expression of PINK1,Parkin,LC3-Ⅱ,and Beclin1(P＜0.05).Compared with the model group,both the GTW and valsartan groups exhibited decreased mRNA and protein expression of fasting blood glucose,24-hour urinary protein,serum creatinine,urea nitrogen levels,and HIF-1α(P＜0.05),and increased body mass and mRNA/protein expression of PINK1,Parkin,LC3-Ⅱ,and Beclin1(P＜0.05).Conclusion GTW alleviates renal injury and improves renal function in diabetic rats,potentially by activating mitophagy through regulation of the HIF-1α/PINK1/Parkin pathway.关键词
雷公藤多苷/糖尿病肾病/缺氧诱导因子1α/同源性磷酸酶张力蛋白诱导激酶1/帕金森病蛋白通路/线粒体自噬/大鼠Key words
Tripterygium wilfordii multi-glycosides/diabetic nephropathy/HIF-1α/PINK1/Parkin pathway/mitophagy/rats分类
医药卫生引用本文复制引用
李培嘉,宋纯东,王旭,梁爽,郭笑笑,张冲,王墨..基于HIF-1α/PINK1/Parkin通路探讨雷公藤多苷对糖尿病肾病大鼠的影响[J].中药新药与临床药理,2025,36(12):2044-2050,7.基金项目
国家自然科学基金项目(82074493) （82074493）
河南省卫健委国家中医临床研究基地科研专项(2022JDZX003) （2022JDZX003）
河南省中医药科学研究重大专项(2023ZYZD02) （2023ZYZD02）
河南省中医药学科领军人才项目(豫卫中医函(2021)8号) （豫卫中医函(2021）
河南省"双一流"创建工程项目(HSRP-DFCTCM-2023-3-07). （HSRP-DFCTCM-2023-3-07）
