Er-xian ameliorates myocardial ischemia-reperfusion injury in rats through RISK pathway involving estrogen receptors  

作　　者：QIANG Mingmin HAO Jiping LIU Huihui YIN Jia ZHANG Hui YANG Jinxin MENG Hudie CHEN Yuqing GAO Yuqin 

机构地区：[1]College of Medicine,Yan'an University,Yan'an 716000,China [2]Department of Ultrasound Medicine,Ninth Hospital of Xi'an Affiliated to Xi'an Jiaotong University,Xi'an 710054,China [3]Department of Cardiology,Ninth Hospital of Xi'an Affiliated to Xi'an Jiaotong University,Xi'an 710054,China

出　　处：《Chinese Journal of Natural Medicines》2022年第12期902-913,共12页中国天然药物（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.81673787);the Science and Technology Plan Project of Xi'an City(No.2019114813YX003SF036-3);Scientific research project of Xi'an Health Committee(No.2021yb43).

摘　　要：Curculigo orchioides(CUR)and Epimedium(EPI)are traditional Chinese medicines with estrogen-like biological activity,called Xianmao and Xianlingpi(Er-xian)in Chinese.However,whether Er-xian exerts protective effects on myocardial ischemia-reperfusion injury(MIRI)is unknown.This study aimed to investigate the cardioprotective effects of Er-xian preconditioning against MIRI and the underlying mechanisms.CUR or EPI was administered intragastrically to aged female rats as a monotherapy or combination therapy.2 weeks later,a rat MIRI model was established.Myocardial infarction size,myocardial morphology,cTnT,cell apoptosis rate,intracellular calcium concentration,mitochondrial permeability transition pore(MPTP)opening and reperfusion injury salvage kinase(RISK)signaling pathway molecules were observed after the surgery.To evaluate the mechanisms of Er-xian,estrogen receptors antagonists ICI 182780 and G15 were used.In this study,Er-xian notably alleviated myocardial tissue damage,maintained mitochondrial morphology,reduced infarct size and cardiac markers,and increased sera levels of E2.Moreover,Er-xian inhibited calcium overload and mPTP opening,and decreased cardiomyocyte apoptosis.We found that the dual therapy of CUR and EPI elicited more noticeable results than CUR or EPI monotherapy.The significant protective effects of Er-xian on ischemia-reperfusion myocardium were attributed to the up-regulation of AKT,ERK1/2 and GSK-3βphosphorylation levels.The cardioprotective effects of Er-xian were significantly reduced after estrogen receptor blockade,especially GPER30.These results indicate that Er-xian attenuates MIRI through RISK signaling pathway and estrogen receptors are the critical mediators.

关 键 词：Er-xian Curculigo orchioides EPIMEDIUM Myocardial ischemia-reperfusion injury Estrogen receptors RISK pathway 

分 类 号：R965[医药卫生—药理学]