基于内质网应激-自噬crosstalk探讨虎杖苷对糖尿病肾病足细胞损伤的保护作用  

To investigate the protective effect of polydatin on podocellular injury in diabetic nephropathy based on endoplasmic reticulum stress-autophagy crosstalk

作　　者：冯健华 黄增光 莫志辉 FENG Jian-Hua;HUANG Zeng-Guang;MO Zhi-Hui(General Practice Department,the Fifth Affiliated Hospital of Southern Medical University,Guangzhou 510900,Guangdong,China)

机构地区：[1]南方医科大学第五附属医院全科医学科,广东广州510900 [2]南方医科大学第五附属医院呼吸内科,广东广州510900 [3]南方医科大学第五附属医院消化内科,广东广州510900

出　　处：《吉林医学》2025年第3期509-513,共5页Jilin Medical Journal

基　　金：广东省中医药局科研项目[项目编号:20221266]。

摘　　要：目的:基于内质网应激-自噬crosstalk探讨虎杖苷对糖尿病肾病(DN)足细胞损伤的保护作用。方法:选取30只健康C57BL/6J小鼠,随机分为正常对照组、DN模型组、自噬抑制剂(3-MA)组、自噬激动剂(RAPA)组、低剂量虎杖苷组、高剂量虎杖苷组,每组各5只。除正常对照组外,其他组小鼠用高糖诱导建立DN模型,造模成功后,正常对照组、DN模型组给予等体积生理盐水灌胃,3-MA组给予自噬抑制剂干预,RAPA组给予自噬激动剂干预,低剂量虎杖苷组给予75 mg/kg虎杖苷干预,高剂量虎杖苷组给予150 mg/kg虎杖苷干预。对比各组小鼠的血糖指标、肾功能损伤指标以及自噬相关基因Beclin-1(Beclin-1)、自噬相关5同源物(Atg5)、微管相关蛋白1轻链3Ⅱ型/Ⅰ型(LC3Ⅱ/Ⅰ)、泛素结合蛋白P62(P62)等自噬标志蛋白的mRNA表达和蛋白表达。结果:空腹血糖(FBG)、稳态模型胰岛素抵抗指数(HOMA-IR)相比,正常对照组<高剂量虎杖苷组<低剂量虎杖苷组<RAPA组<3-MA组<DN模型组,差异有统计学意义(P<0.05)。血肌酐(Scr)、尿素氮(BUN)、尿微量白蛋白(mAlb)相比,正常对照组<高剂量虎杖苷组<低剂量虎杖苷组<RAPA组<3-MA组<DN模型组,差异有统计学意义(P<0.05)。Beclin-1、Atg5、LC3Ⅱ/Ⅰ、P62的mRNA相对表达量及其蛋白表达量相比,正常对照组<高剂量虎杖苷组<低剂量虎杖苷组<RAPA组<3-MA组<DN模型组,差异有统计学意义(P<0.05)。结论:虎杖苷能够降低血糖,改善肾功能,减轻糖尿病肾病足细胞损伤,其机制可能与抑制内质网应激所致的自噬有关。Objective To investigate the protective effect of polydatin on podocyte injury in diabetic nephropathy(DN)through the interplay between endoplasmic reticulum stress and autophagy.Methods Thirty C57BL/6J mice were randomly divided into six groups:normal control group,DN model group,autophagy inhibitor(3-MA)group,autophagy agonist(RAPA)group,low-dose polydatin group and high-dose polydatin group,with five mice in each group.After successful modeling,the normal control group and DN model group received equal volumes of normal saline via intragastric administration.The 3-MA group received autophagy inhibitor intervention,the RAPA group received autophagy agonist intervention,the low-dose polydatin group received 75 mg/kg of polydatin,and the high-dose polydatin group received 150 mg/kg of polydatin.The blood glucose index,renal function injury index,and the mRNA and protein expression levels of autophagy marker proteins such as Beclin-1,Atg5,LC3Ⅱ/Ⅰ,and P62 were compared among the groups.Results The fasting blood glucose(FBG)and homeostasis model assessment of insulin resistance(HOMA-IR)values were significantly lower in the normal control group than those of the high-dose polydatin group,which were lower than those of the low-dose polydatin group,the RAPA group,the 3-MA group and DN model group(P<0.05).Similarly,the ratios of serum creatinine(Scr),urea nitrogen(BUN),and urinary microalbumin(mAlb)followed the same trend.The normal control group had the lowest values and the DN model group had the highest(P<0.05).The relative mRNA expression levels and protein expression ratios of Beclin-1,Atg5,LC3Ⅱ/Ⅰ,and P62 also showed a significant decrease from the normal control group to the DN model group,with the polydatin-treated groups falling in between(P<0.05).Conclusions Polydatin could reduce blood glucose levels,improve renal function,and alleviate podocyte injury in diabetic nephropathy.Its mechanism might be related to inhibiting autophagy induced by endoplasmic reticulum stress.

关 键 词：糖尿病肾病 足细胞 虎杖苷 内质网应激 自噬 

分 类 号：R587[医药卫生—内分泌]