大剂量阿托伐他汀对大鼠心肌梗死后心室重构的影响

Influence of large dose atorvastatin on ventricular remodeling in rats after myocardial infarction

目的:探讨大剂量阿托伐他汀治疗对大鼠心肌梗死后心室重构的影响。方法:将48只雄性SD大鼠随机均分为心肌梗死对照组(以去离子水灌胃)、常规剂量组(阿托伐他汀20mg/kg,在建立心肌梗死模型前后4周灌胃给药)和大剂量组(阿托伐他汀80mg/kg,给药方式同常规剂量组)。梗死后2d,采用苏木素伊红染色检测心肌组织病理变化,4周后采用Masson染色评价心肌纤维化,心脏彩超评价心腔大小和心脏功能,并进行各组间比较。结果:病理变化:梗死后2d,心肌梗死对照组着色深浅不均匀;肌纤维排列紊乱,有大片胶原纤维,有部分肌溶灶;常规剂量组着色深浅欠均匀,肌纤维排列不规则,胶原纤维较少,少数肌溶灶;而大剂量组着色深浅略不均匀,肌纤维排列尚规则,极少肌溶灶,且4周后仍有较多存活心肌,心肌细胞间隙见少量胶原纤维。左室结构与功能变化:与心肌梗死对照组,常规剂量组相比,大剂量组左室舒张末期容积[LVEDd,(7.68±0.54)ml比(7.06±0.68)ml比(6.37±0.40)ml]明显减小,左室射血分数[LVEF,(33.0±7.9)%比(39.3±2.8)%比(48.7%±9.1)%]明显提高(P<0.05或<0.01);而心肌梗死对照组与常规剂量组间LVEDd,LVEF均无显著差异(P分别为0.059,0.146)。结论:大剂量阿托伐他汀能显著减轻梗死后心室重构。

Objective：To explore influence of large dose atorvastatin therapy on ventricular remodeling in rats after myocardial infarction.Methods：A total of 48 male SD rats were randomly and equally divided into myocardial infarction（MI）control group（received deionized water gavage）,routine dose group（received atorvastatin 20mg/kg gavage four weeks before and after MI model was established）and large dose group（received atorvastatin 80mg/kg,in the same way as routine dose group）.On two days after MI,hematoxylin eosin（HE）staining was used to detect pathological changes of myocardial tissue;four weeks later,Masson staining was used to evaluate myocardial fibrosis while echocardiography was used to assess cardiac chamber size and heart function,the results were compared among three groups.Results：Pathologic change：On two days after MI,color of stained myocardial tissue was uneven,muscular fiber arranged in turbulence,there were partial dissolved muscle focus and blockbuster collagenous fiber in MI control group;color of stained myocardial tissue was lack of even,arrangement of muscular fiber was irregular,there were less dissolved muscle focus and collagenous fiber in routine dose group;color of stained myocardial tissue was slightly uneven,muscular fiber still arranged in rules and there was very few dissolved muscle focus and still more survived myocardium in infarct area,and small amount of collagen fibrosis was found in myocardial cell clearance after four weeks in large dose group.Change of left ventricular structure and function：Compared with MI control group and routine dose group,the left ventricular end-diastolic dimension[LVEDd,（7.68±0.54）ml vs.（7.06±0.68）ml vs.（6.37±0.40）ml]significantly reduced in large dose group,left ventricular ejection fraction[LVEF,（33.0±7.9）% vs.（39.3±2.8）% vs.（48.7%±9.1）%]significantly rose（P〈0.05,or0.01）;but those indexes no significant difference between MI control group and routine dose group（P=0.059,0.146respectively）.Conclusion：Large dose atorvastatin may significantly relieve ventricular remodeling after infarction.