Effect of Qishen Yixin Granules on microcirculatory endothelial dysfunction induced by Ang Ⅱ and high-fat diet in mice and its mechanism
- VernacularTitle:芪参益心颗粒对Ang Ⅱ联合高脂诱导小鼠微循环血管内皮功能障碍的改善作用及机制
- Author:
Wen-fang JIN
1
;
Zhen-ni ZHANG
;
Tian-tian ZHU
;
Hu-gang JIANG
;
Xin-qiang WANG
;
Chun-zhen REN
;
Xi-ping XING
;
Kai LIU
;
Ying-dong LI
;
Xin-ke ZHAO
Author Information
- Publication Type:Journal Article
- Keywords: endothelial dysfunction; Nrf2/HO-1 sig-naling pathway; Qishen Yixin granules; oxidative stress; Ang Ⅱ; mechanism of action
- From: Chinese Pharmacological Bulletin 2025;41(10):1982-1990
- CountryChina
- Language:Chinese
- Abstract: Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.
