阿魏酸川芎嗪对大鼠心肌缺血再灌注损伤的保护作用及分子机制研究  

Protective Effects and Molecular Mechanism of Ligustrazine and Ferulate on Myocardial Ischemia-reperfusion Injury in Rats

作　　者：赵润英[1] 郝伟[1] 孟祥军[1] 赵丽妮[1] 李昭[1] 王俊平[1] 丁双双 魏巍 

机构地区：[1]沈阳医学院,沈阳110034 [2]沈阳博瑞生物技术有限公司,沈阳110034

出　　处：《中国实验方剂学杂志》2012年第19期230-234,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：沈阳市科技局科技计划项目(F10-149-9-16)

摘　　要：目的:观察阿魏酸川芎嗪对大鼠心肌缺血再灌注损伤的影响,并探讨其可能的分子机制。方法:将60只雄性SD大鼠随机分成5组:假手术组、缺血再灌注组、川芎嗪(4 mg.kg-1)组、阿魏酸川芎嗪低剂量(4 mg.kg-1)组、阿魏酸川芎嗪高剂量(8 mg.kg-1)组;采用结扎左冠状动脉前降支30 min、再灌注120 min的方法复制大鼠心肌缺血再灌注模型;各组大鼠于再灌注前10 min分别颈iv给药;于再灌注结束后,进行血清生化学指标及心肌组织学检测。结果:阿魏酸川芎嗪能显著降低血清中肌酸激酶同功酶(CK-MB)、乳酸脱氢酶(LDH)和心肌钙蛋白I(cTnI)、丙二醛(MDA)的水平,提高总超氧化物歧化酶(T-SOD)活性,缩小心肌梗死范围,增加Bcl-2蛋白的表达,减少Bax蛋白的表达,降低Bcl-2/Bax的比值和心肌细胞凋亡指数,与缺血再灌注组比较,差异有统计学意义(P<0.01);阿魏酸川芎嗪部分指标优于川芎嗪(P<0.05),且呈现剂量依赖性。结论:阿魏酸川芎嗪对大鼠心肌缺血再灌注损伤具有良好保护作用;阿魏酸川芎嗪抗心肌细胞凋亡的机制可能与其上调Bcl-2基因和下调Bax基因表达有关。Objective：To observe the protective effect of ligustrazine and ferulate on myocardial ischemia-reperfusion injury and probe into its possible molecular mechanism in rats.Method：Sixty male rats were randomly divided into five groups：sham-operation group,ischemia-reperfusion group,ligustrazine（4 mg · kg-1） group,ligustrazine＋ferulate low dose（4 mg · kg-1） group,ligustrazine＋ferulate high dose（8 mg · kg-1） group.The rat model with ischemia-reperfusion injury was established with 30 min of myocardial ischemia and followed by 120 min reperfusion.The rats were treated for 10 min before reperfusion through jugular vein injection.After the reperfusion was finished,the biochemical indicators in serum and histological index in myocardium were investigated.Result：Compared with ischemia-reperfusion group,ligustrazine and ferulate could lower the level of creatine kinase isoenzyme（CK-MB）,lactate dehydrogenas（LDH）,cardiac troponin I（cTnI） and malondialdehyde（MDA） in blood,increase the activity of total-superoside dismutase（T-SOD） in blood,reduce the myocardial infarction size,increase the expression of Bcl-2 protein,decrease the expression of Bax protein,reduce the myocardial apoptosis index and Bcl-2/Bax ratio（P0.01）;all indicators for ligustrazine and ferulate showed dose-dependently superior to ligustrazine（P0.05或P0.01）.Conclusion：Ligustrazine and ferulate had a well protective effect on rats with myocardial ischemia-reperfusion injury.Anti-apoptotic effect was related to up-regulate the expression of Bcl-2 and down-regulate the expression of Bax by ligustrazine and ferulate.

关 键 词：阿魏酸川芎嗪 心肌缺血再灌注损伤 细胞凋亡 BCL-2基因 BAX基因 

分 类 号：R285.5[医药卫生—中药学]