Corilagin alleviates podocyte injury in diabetic nephropathy by regulating autophagy via the SIRT1-AMPK pathway  

作　　者：Yu Lou Yu-Ting Luan Wen-Qing Rong Yun Gai 

机构地区：[1]Department of Preventive Treatment of Disease,Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200137,China [2]Department of Infectious Diseases,Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200137,China [3]Department of General Practice(Including Medical Oncology),Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200137,China

出　　处：《World Journal of Diabetes》2024年第9期1916-1931,共16页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by Shanghai Pudong New Area Leading Talents Training Program Project,No.PWR12020-02;Shanghai Pudong New Area Excellent Young Medical Talents Training Program Project,No.PWRq2023-40;Shanghai Pudong New Area Health and Family Planning Scientific Research Project,No.PW2022A-91.

摘　　要：BACKGROUND Diabetic nephropathy(DN)is the most frequent chronic microvascular consequence of diabetes,and podocyte injury and malfunction are closely related to the development of DN.Studies have shown that corilagin(Cor)has hepatoprotective,anti-inflammatory,antibacterial,antioxidant,anti-hypertensive,antidiabetic,and anti-tumor activities.AIM To explore the protective effect of Cor against podocyte injury in DN mice and the underlying mechanisms.METHODS Streptozotocin and a high-fat diet were combined to generate DN mice models,which were then divided into either a Cor group or a DN group(n=8 in each group).Mice in the Cor group were intraperitoneally injected with Cor(30 mg/kg/d)for 12 wk,and mice in the DN group were treated with saline.Biochemical analysis was used to measure the blood lipid profiles.Hematoxylin and eosin staining was used to detect pathological changes in kidney tissue.Immunohistochemistry and Western blotting were used to assess the protein expression of nephrin and podocin.Mouse podocyte cells(MPC5)were cultured and treated with glucose(5 mmol/L),Cor(50μM),high glucose(HG)(30 mmol/L),and HG(30 mmol/L)plus Cor(50μM).Real-time quantitative PCR and Western blotting RESULTS Compared with the control group,the DN mice models had increased fasting blood glucose,glycosylated hemoglobin,triglycerides,and total cholesterol,decreased nephrin and podocin expression,increased apoptosis rate,elevated inflammatory cytokines,and enhanced oxidative stress.All of the conditions mentioned above were alleviated after intervention with Cor.In addition,Cor therapy improved SIRT1 and AMPK expression(P<0.001),inhibited reactive oxygen species and oxidative stress,and elevated autophagy in HG-induced podocytes(P<0.01).CONCLUSION Cor alleviates podocyte injury by regulating autophagy via the SIRT1-AMPK pathway,thereby exerting its protective impact on renal function in DN mice.

关 键 词：CORILAGIN Podocyte injury Diabetic nephropathy AUTOPHAGY High glucose SIRT1-AMPK pathway 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]