摘要
目的探讨雷公藤多苷(GTW)通过调控缺氧诱导因子1α(HIF-1α)/同源性磷酸酶张力蛋白诱导激酶1(PINK1)/帕金森病蛋白(Parkin)信号通路对糖尿病肾病大鼠肾损伤的影响。方法高脂高糖饮食联合小剂量链脲佐菌素(STZ)建立糖尿病肾病大鼠模型,将造模成功的大鼠按照随机数字表法分为模型组、雷公藤多苷组和缬沙坦(代文)组,另设置空白组。雷公藤多苷组大鼠灌胃6.25 mg·kg^(-1)雷公藤多苷,缬沙坦组大鼠灌胃8.33 mg·kg^(-1)缬沙坦,空白组和模型组大鼠灌胃等量生理盐水,每日1次,连续6周。测定大鼠空腹血糖水平、24 h尿蛋白和体质量,全自动生化分析仪检测血肌酐、尿素氮含量,HE染色观察肾组织病理损伤,qRT-PCR法和蛋白印迹法分别检测HIF-1α、PINK1、Parkin、LC3-Ⅱ和Beclin1mRNA和蛋白表达量。结果与空白组比较,模型组大鼠空腹血糖和24 h尿蛋白含量、血肌酐和尿素氮含量、HIF-1αmRNA和蛋白表达量升高(P<0.05),体质量及PINK1、Parkin、LC3-Ⅱ和Beclin1 mRNA和蛋白表达量降低(P<0.05);与模型组比较,雷公藤多苷组和缬沙坦组大鼠空腹血糖和24h尿蛋白含量、血肌酐和尿素氮含量、HIF-1αmRNA和蛋白表达量降低(P<0.05),体质量及PINK1、Parkin、LC3-Ⅱ和Beclin1 mRNA和蛋白表达量升高(P<0.05)。结论雷公藤多苷可减轻糖尿病大鼠肾损伤,改善肾功能,其机制可能是通过调控HIF-1α/PINK1/Parkin通路激活线粒体自噬发挥作用。
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.
作者
李培嘉
宋纯东
王旭
梁爽
郭笑笑
张冲
王墨
LI Peijia;SONG Chundong;WANG Xu;LIANG Shuang;GUO Xiaoxiao;ZHANG Chong;WANG Mo(Department of Pediatrics,The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450046 Henan,China;School of Pediatrics,Henan University of Chinese Medicine,Zhengzhou 450000 Henan,China;Children’s Hospital of Chongqing Medical University,Chongqing 400015,China)
出处
《中药新药与临床药理》
北大核心
2025年第12期2044-2050,共7页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家自然科学基金项目(82074493)
河南省卫健委国家中医临床研究基地科研专项(2022JDZX003)
河南省中医药科学研究重大专项(2023ZYZD02)
河南省中医药学科领军人才项目(豫卫中医函(2021)8号)
河南省“双一流”创建工程项目(HSRP-DFCTCM-2023-3-07)。
