肉蔻五味及卡托普利对大鼠心肌梗死模型中MMPs和c-myc表达的影响

目的:探讨肉蔻五味丸及卡托普利对大鼠心肌梗死模型中基质金属蛋白酶(MMPs)和原癌基因c-myc表达的影响。方法:96只SD大鼠,随机抽取6只作为正常对照组(C0)。余下90只腹腔注射异丙基肾上腺素制备心肌梗死模型(MI),然后随机平分为5组:模型对照组(Ct);卡托普利组(Cap),卡托普利50mg/kg.d灌胃;肉蔻五味丸低(RKl)、中(RKm)、高(RKh)剂量组,分别给予肉蔻五味丸0.2g/kg.d、0.5g/kg.d、1.0g/kg.d灌胃。各MI组在开始灌胃后1、7、28d分别处死6只。计算左室重量指数,酶谱法测心肌MMPs活性,RT-PCR法检测心肌c-myc mRNA的表达。结果:MI组左室重量指数高于C0组,心肌MMP-2、MMP-9活性、c-myc表达在各时段明显强于C0组。而Cap组和RKh组左室重量指数、MMPs活性均显著低于Ct组(P<0.05或P<0.01),c-myc mRNA表达减弱。结论:大鼠心肌梗死后心肌MMP-2、MMP-9活性升高及原癌基因c-myc在早期表达增强,是心室重构的重要原因之一。卡托普利和肉蔻五味丸对MMPs活性及c-myc表达有抑制作用,可能是其治疗心肌梗死后左室重构的机制之一。

EFFECT OF ROUKOUWUWEI AND CAPTOPRIL ON MMPS AND C- MYC EXPRESSION IN RODENT MI MODEL

Objective:To investigate the effect of RouKouWuWei and Captopril on matrix metolloproteinases(MMPs) and proto-oncogene c-myc expression in rodent model of myocardial infarction(MI).Methods:96 male SD rats were used in the study,six as normal control(C0),90 as MI model by intraperitoneal application of isoproterenol(ISO),which were further randomly divided into 5 groups with 18 rats each:control(Ct),without any treatment;Cap group,treated with Captopril(50mg/kg)orally;RKl,RKm and RKh groups,treated with RowKouWuWei pills in low,mid and high dosages(0.2,0.5 and 1.0g/kg)respectively.On day 1,7 and 28,6 were sacrificed each time and left ventricular weight index was calculated;MMPs measured by zymography;c-myc mRNA semi-quantified by RT-PCR.Results:Left ventricular weight index,bioactivity of MMP-2,MMP-9 and c-myc expression were increased significantly in rat MI models compared with C0;while the parameters decreased in Cap and RKh groups compared with Ct(P<0.05 or P<0.01).Conclusion:MMPs and c-myc expression increased in rat MI model,which may be one of the major causes of ventricular remodeling in MI;Captopril and RouKouWuWei Pill could suppress the expression of MMPs and c-myc and may be one of the mechanisms in MI treatment.