美托洛尔对小鼠心肌缺血再灌注损伤的保护机制研究  

Protective effect of metoprolol on ischemia-reperfusion induced myocardial tissue injury in mice

作　　者：李强[1,2] 陈海燕[1] 胡厚祥[1] 徐继前[1] 谭春燕[1] 徐磊[1] 张双[1] 王欢[1] 张荣驿 岳荣川[1] 罗涛[1] 

机构地区：[1]川北医学院附属医院心内科,四川南充637000 [2]重庆市南川区人民医院心内科,408400

出　　处：《重庆医学》2016年第3期317-319,共3页Chongqing medicine

基　　金：国家自然科学基金项目(81070101);四川省教育厅课题(12ZA060)

摘　　要：目的探讨美托洛尔对心肌缺血再灌注损伤保护作用的机制。方法取健康3~4个月雄性C57BL/6小鼠32只,分为4组（n=8）,即对照组、美托洛尔组、缺血再灌注组（I/R组）和美托洛尔＋缺血再灌注组（美托洛尔＋I/R组）。检测各组小鼠心肌损伤情况、心肌细胞凋亡率、细胞色素c（Cyt C）的释放、半胱氨酸天冬氨酸蛋白酶3（Caspase-3）活性及钙蛋白酶（calpain）活性。结果与I/R组相比,美托洛尔预处理后,显著减少了心肌梗死区与缺血危险区域的比率（P〈0.05）,而心肌缺血危险区域与左心室的比率并无明显变化;与对照组相比,I/R组心肌细胞凋亡率、心肌组织Cyt C的释放、Caspase-3活性及calpain活性均明显增高（P〈0.01）,美托洛尔预处理能抑制I/R损伤引起的上述变化。结论美托洛尔可能通过抑制心肌细胞内calpain的活化,从而抑制心肌细胞凋亡,最终减轻心肌的I/R损伤。Objective To investigate the possible mechanism of metoprolol on protecting against ischemia-reperfusion in duced injury. Methods A total of 32 healthy 3-4 months male C57BL/6 mice were divided into four groups（n=8）as following： Sham-operating group（control group）;metoprolol group;ischemia-reperfusion group（I/R group） ;metoprolol＋ I/R group. Myo- cardial injury,apoptosis,cytochrome c release,Caspase-3 activity and calpain activity were determined in these groups. Results Al- though there was no obvious changes in the regions at risk between I/R group and metoprolol ＋ I/R group,metoprolol pretreat- ment significantly reduced the ratio of the infarct to risk regions（P〈0.05）. In the I/R group,the rate of cardiomyocyte apoptosis, cytochrome c release,as well as the activity of Caspase-3 and calpain significantly increased compared to the control group（P〈 0.01）. However,these effects of I/R injury were alleviated by pretreatment with metoprolol. Conclusion metoprolot might protect against ischemia-reperfusion induced injury by preventing calpain activation.

关 键 词：心肌 心肌缺血 心肌再灌注 美托洛尔 钙蛋白酶 细胞凋亡 

分 类 号：R96[医药卫生—药理学]