海南医科大学学报2026，Vol.32Issue(11)：845-853,9.DOI:10.13210/j.cnki.jhmu.20250519.001
芪蒡糖肾方调控Nrf2/Gpx4通路改善糖尿病肾病肾纤维化的机制研究
Mechanism of Qibang Tangshen Formula improving renal fibrosis in diabetic nephropathy via regulating the Nrf2/Gpx4 pathway
摘要
Abstract
Objective:To investigate the protective effect of Qibang Tangshen Formula(QBTSF)on diabetic nephropathy mice and high glucose-induced fibrosis of human renal cortical proximal tubular epithelial cells HK2.Methods:(1)In vivo experi-ments:C57BL/6 J male mice were selected to establish an animal model of diabetic nephropathy by using high-sugar and high-fat feed+streptozocin injection,and after successful modeling,the mice were divided into a normal group,a model group,a dapa-gliflozin group,a QBTSF low-dose group,a QBTSF middle-dose group,and a QBTSF high-dose group.The drug was adminis-tered continuously for 12 weeks,and the levels of 24 h urinary protein(24 hpro),serum creatinine(Scr),fasting blood glucose(FBG),and ferrous ion(Fe2+)in renal tissues were measured in each group.Masson staining was used to observe the degree of renal histopathological damage.Western blot was used to detect the expression levels of Nrf2/Gpx4 signaling pathway and down-stream fibrosis-related proteins.(2)In vitro experiments:CCK-8 was used to detect cell viability and screen the optimal interven-tion concentration of QBTSF.Western blot was used to detect the expression level of Col3a1 and determine the modeling condi-tions.The HK2 cells were divided into a normal group,a high glucose group,a QBTSF group,and a dapagliflozin group.The in-tracellular concentrations of malondialdehyde(MDA),glutathione(GSH),Fe2+,and reactive oxygen species(ROS)were mea-sured,and the expression levels of Nrf2/Gpx4 signaling pathway and fibrosis-related proteins were analyzed.Transmission elec-tron microscopy was used to observe the ultrastructural changes of HK2 cells.Results:(1)In vivo experiment:Compared to the model group,after the intervention of QBTSF,24 hpro,FBG,Scr,and Fe2+levels in renal tissues were decreased(P＜0.01).In addition,QBTSF could promote the expression of Nrf2,Gpx4,E-Cadherin,and Slc7a11 proteins,as well as reduce the ex-pression of α-SMA、Col3a1,and Vimentin proteins in renal tissues(P＜0.05).(2)In vitro experiments:Compared to the high glucose group,QBTSF could significantly reduce intracellular MDA,Fe2+,and ROS concentrations and improve mitochondrial damage while increasing intracellular GSH content(P＜0.01).In addition,QBTSF promoted the expression of intracellular Nrf2,Gpx4,Slc7a11,and E-Cadherin proteins,while inhibiting the expression of α-SMA,Col3a1,and Vimentin proteins(P＜0.01).Conclusion:QBTSF helps to improve renal fibrosis in diabetic nephropathy,which may be associated with the activation of Nrf2/Gpx4 signaling pathway.关键词
芪蒡糖肾方/纤维化/铁死亡/HK2Key words
Qibang Tangshen Formula/Fibrosis/Ferroptosis/HK2分类
医药卫生引用本文复制引用
徐睿,雍军,郭小平,王琳..芪蒡糖肾方调控Nrf2/Gpx4通路改善糖尿病肾病肾纤维化的机制研究[J].海南医科大学学报,2026,32(11):845-853,9.基金项目
This study was supported by the Health Industry Special Project of Pudong New District Health Commission,Shanghai(PW2023E-03) （PW2023E-03）
Shanghai TCM Three-Year Action Plan(2021-2023)for Advancing Inheritance,Innovation,and Development[ZY(2021-2023)-0403] 上海市浦东新区卫生健康委员会卫生行业专项(PW2023E-03) （2021-2023）
上海市中医药管理局上海市进一步加快中医药传承创新发展三年行动计划(2021年～2023年)[ZY(2021-2023)-0403] （2021年～2023年）
