Effects of Qizhi Tongluo Formula on renal injury in db/db mice via Nrf2/Keap1/ARE signaling pathway
10.3969/j.issn.1001-1528.2025.01.011
- VernacularTitle:基于Nrf2/Keap1/ARE信号通路探讨芪蛭通络方对db/db小鼠肾损伤的影响
- Author:
Bing YANG
1
;
Yao ZHANG
;
Jing-yu MAO
;
Miao TANG
;
Feng-wen YANG
;
Hong-hong WU
;
Jin-chuan TAN
Author Information
1. 河北中医药大学,河北石家庄 050200;河北中医药大学第一附属医院,河北石家庄 050011
- Publication Type:Journal Article
- Keywords:
Qizhi Tongluo Formula;
diabetic kidney disease;
renal injury;
db/db mice;
oxidative stress;
Nrf2/Keap1/ARE signaling pathway
- From:
Chinese Traditional Patent Medicine
2025;47(1):73-80
- CountryChina
- Language:Chinese
-
Abstract:
AIM To investigate the renal protective effects of Qizhi Tongluo Formula on a mouse model of diabetic nephropathy.METHODS The male db/db mice were randomly divided into the model group,the dapagliflozin group(0.76 mg/kg)and the low,medium and high dose Qizhi Tongluo Formula groups(7.83,15.65 and 31.3 g/kg),with 6 mice in each group,in contrast to the 6 db/m mice of the control group.When the mice of the control group and the model group were given distilled water by gavage,those of the other administration groups were dosed with the corresponding drug by gavage once daily for 8 weeks.After the drug administration,the mice had their levels of FBG,BUN,Scr and 24 h-UTP detected;their renal pathological changes observed by transmission electron microscopy(TEM)and HE staining;their levels of serum Nrf2,HO-1,Keap1 and renal oxidative stress assessed by ELISA;their renal Nrf2 protein expression observed by immunofluorescence(IF);their renal protein expressions of Nrf2,HO-1 and Keap1 detected by Western blot;and their renal Nrf2,HO-1,and Keap1 mRNA expressions detected by RT-qPCR.RESULTS Compared with the control group,the model group displayed increased levels of 24 h-UTP,Scr,FBG and renal MDA(P＜0.01);decreased renal activities of SOD,CAT and GSH-Px(P＜0.01);mild glomerular mesangial hyperplasia,vacuolated renal tubular epithelial cells,widely fused podocyte foot processes,disappearance of tear film,decreased secretion levels of serum Nrf2 and HO-1 and renal protein and mRNA expressions of Nrf2 and HO-1(P＜0.05,P＜0.01);and decreased secretion levels of serum Keap1 and renal Keap1 protein and mRNA expressions(P＜0.01).Compared with the model group,the high-dose Qizhi Tongluo Formula group demonstrated decreased levels of 24 h-UTP,Scr,FBG and renal MDA(P＜0.01);increased renal activities of SOD,CAT and GSH-Px(P＜0.01);alleviated renal pathological damage,increased secretion levels of serum Nrf2 and HO-1 and renal protein and mRNA expressions of Nrf2 and HO-1(P＜0.01);and increased level of serum Keap1 secretion and renal Keap1 protein and mRNA expressions(P＜0.01).CONCLUSION Qizhi Tongluo Formula can inhibit oxidative stress and alleviate kidney damage in db/db mice by activating Nrf2/Keap1/ARE signaling pathway.
