阿托伐他汀对急性心肌梗死大鼠心肌MPO浓度和TIMP-2/MMP-9表达的影响及其对心功能的保护作用

Effects of Atorvastatin on Concentration of MPO and Expression of TIMP-2/MMP-9 in Left Ventricle,and Preservation of Heart Function after Myocardial Infarction in Rat

【目的】探讨阿托伐他汀对急性心肌梗死大鼠心肌髓过氧化物酶(MPO)浓度、基质金属蛋白酶组织抑制因子-2/基质金属蛋白酶-9(TIMP-2/MMP-9)表达的影响及其对心功能保护作用。【方法】结扎40只雄性SD大鼠左冠状动脉造成急性心肌梗死模型,存活35只随机分为两组。假手术组10只。术后第1天起给予阿托伐他汀灌胃(1mg/kg/d,17只),对照组给予等量生理盐水(18只)。14d后,比较各组大鼠心肌组织MPO浓度、胶原纤维含量、心肌梗死面积、TIMP-2/MMP-9表达量和心功能。【结果】对照组大鼠心肌组织髓过氧化物酶浓度、胶原纤维含量、心肌梗死面积均明显高于阿托伐他汀治疗组(P<0.05),而TIMP-2/MMP-9比值和心功能低于阿托伐他汀治疗组(P<0.05)。【结论】阿托伐他汀可改善急性心梗大鼠心脏重构及心功能,主要是通过减少白细胞浸润、下调MPO浓度和调节TIMP-2/MMP-9表达,从而减少心肌梗死面积及胶原纤维含量。

Objective To investigate the effects of atorvastatin on concentration of MPO and expression of TIMP-2/MMP-9 in left ventricle,and preservation of heart function after myocardial infarction in rat.Methods Acute myocardial infarction was performed by ligating left coronary artery in 40 male Sprague-Dawley rats.Thirty-five survival rats were randomly divided into two groups.Group atorvastatin was gavaged with 1 mg/kg/day atorvastatin（n = 17） and group control was gavaged with equal volume of saline（n = 18） from the first day after myocardial infarction.Fourteen days later,concentration of MPO,fibrosis volume,infarcted area,expression of TIMP-2/MMP-9 and cardiac function were compared with control group.Results Concentration of MPO,fibrosis volume,and infracted area were higher in control group compared with atorvastatin group（P0.05）,while TIMP-2/MMP-9 ratio and cardiac function in control group were lower compared with atorvastatin group（P0.05）.Conclusion Cardiac remodeling and cardiac function were improved by atorvastatin treatment after acute myocardial infarction in rat.The main mechanism is by reducing leukocyte infiltration,down-regulation of myeloperoxidase concentration and regulation of TIMP-2/MMP-2 expression,which attributed to infarcted area and fibrosis volumn decrease.