心痛方对急性心肌梗死大鼠MMP-9 mRNA及TIMP-1 mRNA表达的影响

摘要

目的 通过观察心痛方对大鼠急性心肌梗死(AMI)后基质金属蛋白酶-9(MMP-9)mRNA和金属蛋白酶组织抑制物-1(TIMP-1)mRNA表达及对心肌形态学的影响,探讨心痛方治疗AMI的疗效机制.方法 80只SD大鼠随机分为假手术组、模型组、心痛方组、双抗组(阿司匹林+氯吡格雷),冠脉结扎法制备AMI模型,灌胃给药7d后处死大鼠,运用RT-PCR法测定心肌组织MMP-9 mRNA、TIMP-1 mRNA表达,心肌细胞HE染色观察形态学改变.结果 心痛方能使AMI大鼠心肌内MMP-9 mRNA表达减少(P＜ 0.01);TIMP-1mRNA表达升高(P＜0.01);MMP-9 mRNA/TIMP-1 mRNA比值降低(P＜0.01);心肌损伤程度及心梗面积与MMP-9 mRNA/TIMP-1 mRNA比值呈正直线相关.结论 心痛方对AMI缺血心肌具有保护作用,其作用机制可能与增加TIMP-1 mRNA表达,降低MMP-9 mRNA表达,从而调节MMP-9 mRNA/TIMP-1 mRNA的平衡有关.%Objective:To investigate the effect of Xintong Decoction on the expression of matrix metalloproteinase-9 (MMP-9) mRNA,tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA and effects on myocardial morphology in acute myocardial infarction (AMI) rats,and to explore the therapeutic mechanism of Xintong Decoction on AMI.Methods:80 SD rats were randomly divided into sham operation group (A group),the model group (group B),Xintong De coc tion group (group C),and Dual anti-platelet group (aspirin+clopidogrel,group D).AMI model was established by coronary artery ligation method.Rats were killed 7 days after intragastric administration.Expression of MMP-9 mRNA and TIMP-1 mRNA in myocardium were observed by RT-PCR,and morphological changes were observed by HE staining.Results:Xintong Decoction could reduce the expression of MMP-9 mRNA (P ＜ 0.01),increase the expression of TIMP-1 mRNA (P＜ 0.01),and decrease the ratio of M MP-9 mRNA/TIMP-1 mRNA in AMI rats(P＜0.01).The degree of myocardial injury and the area of myocardial infarction were positively correlated with MMP-9 mRNA/TIMP-1 mRNA ratio.Conclusion:Xintong Decoction has protective effects on AMI ischemic myocardium,and its mechanism may be related to increasing the expression of TIMP-1 mRNA,reducing the expression of MMP-9 mRNA and thus regulating the balance of MMP-9 mRNA/ TIMP-1 mRNA.