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.
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)
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]。
关键词
糖尿病肾病
足细胞
虎杖苷
内质网应激
自噬
Diabetic nephropathy
Podocyte
Polydatin
Endoplasmic reticulum stress
Autophagy
