盐酸曲美他嗪调控自噬对大鼠心肌缺血再灌注损伤的保护作用  

Protective Effect of Trimetazidine against Autophagy-induced Myocardial Ischemia-reperfusion Injury in Rats

作　　者：龙玉莹 葛华[2] 王月[1] 王微[2] 

机构地区：[1]沈阳医学院基础医学院病理学与病理生理学教研室,沈阳110034 [2]沈阳医学院附属中心医院循环科,沈阳110075

出　　处：《中国医科大学学报》2017年第7期656-659,663,共5页Journal of China Medical University

摘　　要：目的观察盐酸曲美他嗪(TMZ)在大鼠心肌缺血再灌注损伤中的作用,及其与自噬相关蛋白微管相关蛋白轻链3蛋白-Ⅱ(LC3-Ⅱ)和自噬流的另一个标志物p62的关系,并探讨其作用机制。方法将54只雄性SD大鼠随机分成假手术组(Sham组)、心肌缺血30 min再灌注组(I/R组)、心肌缺血30 min再灌注药物干预组(I/R+TMZ组),每组18只。制备大鼠在体心肌缺血再灌注损伤模型,于即刻、4周、8周后处死大鼠,实时定量PCR和Western blotting检测心肌组织LC3-Ⅱ和p62的表达水平,HE染色观察心肌组织形态改变。结果与Sham组相比,I/R组大鼠心肌细胞内LC3-Ⅱ和p62的表达水平增高(P<0.05);与I/R组相比,I/R+TMZ组大鼠心肌细胞内LC3-Ⅱ和p62的表达水平降低(P<0.05)。在第4周时心肌细胞中LC3-Ⅱ和p62的表达水平增高(P<0.05);在第8周时心肌细胞中LC3-Ⅱ和p62的表达水平降低(P<0.05)。结论 TMZ的干预可能通过调节自噬流对大鼠损伤的心肌起保护作用,并存在一定的时间效应。Objective To observe the protective effects of trimetazidine against myocardial ischemia-reperfusion （I/R） injury in rats and relation- ship with the autophagy-related protein, microtubule-associated protein hght chain 3 protein- Ⅱ （LC3-Ⅱ） and another autoclaved marker sequestosome 1 （p62） as well as to investigate the mechanism of action. Methods Fifty-four male SD rats were randomly divided into three groups with 18 rats in each group： sham group, myocardial I/R group, and TMZ plus myocardial I/R group. The rats in each group were sacrificed at model completion,and 4 and 8 weeks later. RT- PCR and Western blotting were performed to determine the levels of LC3-Ⅱ and p62. The morphological changes in the myocardium were observed by HE staining. Results Compared with the sham group, the I/R group demonstrated increased expression of LC3-Ⅱ and p62 （P〈 0.05）. Compared with that in the I/R group,the expression of LC3-Ⅱ and p62 in the I/R ＋ TMZ group decreased （ P 〈 0.05 ）. The expression of LC3-Ⅱ and p62 increased at week 4 （P 〈 0.05 ）. At week 8, the expression levels of LC3-11 and p62 decreased in cardiomyocytes （P 〈 0.05）. Conclusion Intervention with trimetazidine may protect the myocardium of rats against ischemia-reperfusion injury by regulating autophagy and the effect is maintained for a certain period.

关 键 词：盐酸曲美他嗪 心肌缺血再灌注损伤 自噬 LC3-Ⅱ P62 

分 类 号：R541.4[医药卫生—心血管疾病] R972.4[医药卫生—内科学]