心宁片对糖尿病合并心肌缺血再灌注损伤的保护作用和机制研究  

Protective Effects and Possible Mechanism of Xinning Pill on Myocardial Ischemia Reperfusion Injury in Diabetes 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,陕西咸阳712000 [2]陕西中医药大学,陕西咸阳712046 [3]第四军医大学药学院新药研发中心,陕西西安710032

出　　处：《现代生物医学进展》2017年第5期835-838,共4页Progress in Modern Biomedicine

基　　金：陕西省科技厅统筹创新工程计划项目(2016KTZDSF01-03-03)

摘　　要：目的:研究心宁片对糖尿病合并心肌缺血再灌注损伤的保护作用及其作用机制。方法:腹腔注射STZ加高脂高糖饲料喂养诱导二型糖尿病小鼠模型,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30 mg·kg^(-1)),每组10只。在此基础上,制作心肌缺血再灌注模型。测定小鼠体内血糖和血脂水平,测定缺血再灌注后心肌酶(LDH和CK-MB)、心梗面积以及AMPK磷酸化水平。结果:心宁片能够有效的控制糖尿病小鼠体内血糖和血脂水平,减轻胰岛素抵抗情况。心宁片能够减轻缺血再灌注引起的心肌梗死,降低LDH和CK-MB水平,减少MDA水平。同时,还发现心宁片能够促进AMPK蛋白磷酸化。采用AMPK特异性抑制剂Compound C抑制AMPK后,LDH水平显著升高,心宁片的心肌保护作用减弱。结论:心宁片能够保护糖尿病合并缺血再灌注损伤,其机制可能是通过AMPK信号通路。Objective： To study the protective effects and possible mechanism of Xinning Pill on myocardial ischemia reperfusion injury in diabetes mouse. Methods： Intraperitoneal injected STZ accompany with high fat and high sugar diet was used to induce type 2diabetes mouse model. The mice were randomly divided into sham group, model group and Xinning Pill group（10, 20 and 30 mg·kg^-1）,and 10 mice in every group. On this basis, the myocardium ischemia and reperfusion model was developed. Fasting blood glucose and blood fats were measured. The LDH and CK-MB levels, infarct area, and phosphorylation levels were tested after myocardium ischemia and reperfusion. Results： Xinning Pill could inhibit the levels of blood glucose and blood lipids, alleviate insulin resistance. Xinning Pill also could alleviate infarct area, decrease the levels of LDH, CK-MB and MDA which rose by myocardium ischemia and reperfusion. We also found that Xinning Pill induced the phosphorylation levels of AMPK. The protective effect of Xinning Pill was abolished by AMPK inhibitor（Compound C）. Conclusions： Xinning Pill can protect myocardial ischemia reperfusion injury in diabetes mouse model, and the possible mechanism might be through AMPK pathway.

关 键 词：心宁片 糖尿病 心肌缺血再灌注 AMPK 

分 类 号：R-33[医药卫生] R587.2