文献类型：期刊文献

中文题名：芪参益心颗粒对AngⅡ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

英文题名：Effect of Qishen Yixin Granules on microcirculatory endothelial dysfunction induced by AngⅡand high-fat diet in mice and its mechanism

作者：靳文芳[1,2];张珍妮[1,2];朱田田[3];蒋虎刚[1,2];王新强[2,4];任春贞[1,2];邢喜平[1];刘凯[1,4];李应东[1,4];赵信科[1,2,4]

第一作者：靳文芳

机构：[1]甘肃中医药大学中西医结合学院,甘肃兰州730000;[2]甘肃中医药大学甘肃省中医方药挖掘与创新转化重点实验室/甘肃省中药新产品创制省级工程实验室,甘肃兰州730000;[3]甘肃中医药大学药学院,甘肃兰州730000;[4]甘肃中医药大学附属医院心血管中心,甘肃兰州730020

第一机构：甘肃中医药大学中西医结合学院

年份：2025

卷号：41

期号：10

起止页码：1982

中文期刊名：中国药理学通报

外文期刊名：Chinese Pharmacological Bulletin

收录：;北大核心:【北大核心2023】；

基金：国家中医药管理局“李应东全国名中医传承工作室”建设项目(国中医药办人教函[2022]5号);甘肃省科技重大专项计划(No 20ZD7FA002);2023年度甘肃省中医药科研课题项目(No GZKP-2023-59)。

语种：中文

中文关键词：血管内皮功能障碍;Nrf2/HO-1信号通路;芪参益心颗粒;氧化应激;AngⅡ;作用机制

外文关键词：endothelial dysfunction;Nrf2/HO-1 signaling pathway;QishenYixin granules;oxidative stress;AngⅡ;mechanism of action

摘要：目的明确芪参益心颗粒通过激活Nrf2/HO-1信号通路调控氧化应激改善小鼠微循环血管内皮功能障碍(vascular endothelial dysfunction,VED)的作用机制。方法C57小鼠随机分为空白组、模型组、阳性药物组、芪参益心颗粒低、中、高剂量组,采用长期输注AngⅡ配合高脂饮食建立小鼠VED模型,各给药组给予相应药物干预4周后,超声心动图检测心功能;Carstairs染色观察心肌组织微血栓形成情况;Heidenhain染色观察心肌缺血情况;电镜观察内皮细胞超微结构;ELISA法检测血清中EMPs、ROS、NO、ET-1、TF、TM、VWF、TXA2含量;化学法检测MDA、SOD、GSH-Px表达量;采用免疫组化染色CD34检测心脏微血管密度及Nrf2、Keap1、HO-1蛋白表达;Western blot法检测心肌组织Keap1、细胞质Nrf2及细胞核Nrf2、HO-1蛋白表达。结果芪参益心颗粒可有效改善小鼠心功能,缓解内皮细胞及内皮功能损伤,上调血清NO水平及SOD、GSH-Px活性,下调ROS及ET-1、VWF、TXA2、TF、TM、EMPs等血管炎症损伤因子表达,增加CD34、Nrf2、HO-1阳性计数及微血管密度,抑制MDA、Keap1、细胞质Nrf2蛋白表达,提升核内蛋白HO-1、Nrf2表达。结论芪参益心颗粒可能通过调控Nrf2/HO-1信号通路,抑制氧化应激、炎症反应,改善VED小鼠血管内皮损伤,从而改善心功能。
Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vascular 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,positive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of AngⅡcombined 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 observe the formation of microthrombi in myocardial tissue.The microvascular ischemia was evaluated by Heidenhain 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 microvascular density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical staining.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.Furthermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tissue,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.