心宁片对小鼠心肌缺血再灌注损伤的保护作用及其机制研究  

Protective effects of Xinning Tablets on myocardial ischemia reperfusion injury in mouse model

作　　者：史志辉 刘洋[2] 肖会敏[3] 何悦[3] 刘海月 杨旭[3] 唐志书[2] 王四旺[3] 

机构地区：[1]陕西君碧莎制药有限公司,咸阳712000 [2]陕西中医药大学,咸阳712046 [3]第四军医大学药学院新药研发中心,西安710032

出　　处：《西北药学杂志》2017年第5期614-618,共5页Northwest Pharmaceutical Journal

基　　金：陕西省新药创制工程技术研究中心心宁片物效基础及其再次开发研究项目(编号:S2014ZDGC106)

摘　　要：目的研究心宁片对小鼠心肌缺血/再灌注损伤(MI/RI)的保护作用和作用机制。方法采用3种体外自由基体系测定心宁片的自由基清除能力。C57小鼠随机分为假手术组、模型组及心宁片高、中、低剂量组(心宁片10,20和30mg·kg-1),每组10只。结扎冠状动脉左前降支制备MI/RI模型,观察给药后小鼠心功能参数,测定体内抗氧化酶水平,Western Blot法检测核因子E2相关因子2蛋白表达。结果心宁片能够有效清除体外自由基,清除能力与维生素C相当。心宁片低、中、高剂量组能够明显改善心功能参数,升高体内抗氧化酶水平,促进核因子E2相关因子2蛋白表达。敲除核因子E2相关因子2蛋白后,心宁片调节氧化酶表达的能力被取消。结论心宁片对MI/RI具有保护作用,其作用机制有可能是通过直接清除自由基和促进核因子E2相关因子2蛋白表达,从而升高抗氧化酶水平。Objective To study the protective effects and possible mechanism of Xinning Tablets on myocardial ischemia reperfusion injury in mouse.Methods Three radical reaction systems were used to test the cleaning radical activity of Xinning Tablets.C57 mice were randomly divided into sham group,model group and Xinning Tablets group（10,20 and 30mg·kg-1）,and 10 mice in each group.The myocardial ischemia reperfusion injury model was induced through occluding the left anterior descending branch of coronary artery.Cardiac parameters and antioxidatant proteins were measured.The protein expression of NF-E2-related factor 2was measured by Western Blot.Results Xinning Tablets could clear radicals in vitro,and the cleaning activity was as good as Vitamin C.Xinning Tablets could improve the cardiac parameters,raise the levels of antioxidatant proteins,induce the expression of NF-E2-related factor 2.These effects were abolished by NF-E2-related factor 2knockdown.Conclusion Xinning Tablets could protect myocardial ischemia reperfusion injury,and the possible mechanism might be through cleaning radicals directly and inducing the expression of NF-E2-related factor 2,thus increasing the expression of several antioxidatant proteins.

关 键 词：心宁片 心肌缺血再灌注损伤 氧化损伤 核因子E2相关因子2 

分 类 号：R965[医药卫生—药理学]