海南医科大学学报2025,Vol.31Issue(22):1688-1695,8.DOI:10.13210/j.cnki.jhmu.20241204.003
基于线粒体自噬探索卡格列净对糖尿病小鼠肾脏损伤的改善作用
Mechanisms of canagliflozin alleviating kidney injury in diabetic mice via mitophagy
摘要
Abstract
Objective:To observe the protective effects of canagliflozin on kidney injury in diabetic mice and to explore the reg-ulatory role of mitophagy,thereby accumulating scientific evidence for the prevention and treatment of diabetic nephropathy.Meth-ods:A total of 24 male C57BL/6J mice,7 weeks old,were randomly divided into the control group,the model group,the con-trol treatment group,and the model treatment group,with 6 mice in each group.The model group received intraperitoneal injec-tions of 55 mg·kg-1·d-1 streptozotocin for 5 consecutive days to establish a diabetic kidney injury model,and the treatment group received 40 mg·kg-1·d-1 canagliflozin via gavage for 12 weeks.Blood glucose levels and body weight changes were recorded for each group.H&E staining was used to observe renal tissue morphology and structure,TUNEL staining and Caspase3 immunohis-tochemistry were employed to assess renal cell apoptosis,and DHE staining was used to determine the level of renal oxidative stress.Western blot and fluorescence staining were used to observe changes in mitophagy-related proteins in the kidneys.Results:Canagliflozin effectively reduced blood glucose levels(P<0.01),restored body weight(P<0.01),reduced renal tissue damage(including swelling,degeneration,and necrosis)(P<0.01),inhibited renal cell apoptosis(P<0.01)and oxidative stress levels(P<0.01),as well as regulated the expression of mitophagy markers LC3 and p62 in renal cells(P<0.01).Conclusion:The pro-tective effects of canagliflozin on diabetic kidney injury involve the regulation of mitophagy.关键词
糖尿病肾病/线粒体/钠-葡萄糖协同转运蛋白2抑制剂/卡格列净/线粒体自噬Key words
Diabetic nephropathy/Mitochondria/SGLT-2 inhibitor/Canagliflozin/Mitophagy分类
医药卫生引用本文复制引用
翁为华,张玄艳,苗倩,张传震,王舒婷,云川,郑运思..基于线粒体自噬探索卡格列净对糖尿病小鼠肾脏损伤的改善作用[J].海南医科大学学报,2025,31(22):1688-1695,8.基金项目
This study was supported by the Natural Science Foundation Project of Hainan Province(821QN403,824QN263) 海南省自然科学基金(821QN403,824QN263) (821QN403,824QN263)