【摘要】 目的采用超声心动图检测评价辛伐他汀对改善大鼠心肌梗死(MI)后心室重构的作用。方法34只大鼠分3组:(1)MI组:仅结扎左冠状动脉前降支(LAD);(2)治疗组:结扎LAD,并用辛伐他汀40 mg.kg-1.d-1进行灌胃;(3)假手术组:开胸,但不结扎LAD。超声心动图检查心脏结构和功能,逆转录-聚合酶链式反应(RT-PCR)测定梗死区和非梗死区肿瘤坏死因子(TNF)-αmRNA表达,免疫印迹法和免疫组织化学染色法测定TNF-α蛋白的产生。结果超声心动图显示,MI组与假手术组比较,左心室舒张末期内径(LVEDd)显著增大,分别为(7.5±0.4)mm和(4.5±0.3)mm,短轴缩短率〔FS,分别为(20.5±2.5)%和(51.6±3.1)%〕和射血分数〔EF,分别为(41.4±4.3)%和(85.2±3.7)%〕明显降低(均为P<0.05)。与MI组比较,辛伐他汀显著减轻左心室扩张,改善左心室功能(P<0.05)。MI组TNF-αmRNA表达和蛋白质的产生较假手术组增加(均为P<0.01),而治疗组TNF-αmRNA表达和蛋白质的产生比MI组明显下降(P<0.05)。TNF-αmRNA表达和蛋白质生成与心功能下降呈正相关,辛伐他汀减轻TNF-α基因表达,改善心功能。结论辛伐他汀改善大鼠MI后心室的不良重塑,其机制可能与降低非梗死区和梗死区心肌内TNF-α基因表达和蛋白质合成有关。更多还原

【Abstract】 Objective To study the effect of simvastatin on improve ventricular remodeling in rats after myocardial infarction（MI）. Methods The MI models of rat were constructed,and divided into three groups:（1）MI group（MI-C）,only ligation of left anterior descending coronary artery（LAD）;（2）Simvastatin group（MI-S）,ligation of LAD and gavage with simvastatin 40 mg·kg^-1·d^-1;（3）Sham group（sham）,no ligation of LAD.Cardiac architecture and function were determined by the echocardiography.The TNF-α mRNA expression in infarction and non-infarction regions was measured by RT-PCR. TNF-α protein was determined by Western blot and immunohistochemical staining.Results The echocardiography showed that the left ventricular end-diastolic diameter（LVEDd,（7.5±0.4）mm versus（4.5±0.3）mm） significantly increased in MI-C group,compared with sham group.The fractional shortening（FS,（20.5±2.5）% versus（51.6±3.1）%） and ejection fraction（EF,（41.4±4.3）%versus（85.2±3.7）%）markedly decreased in MI-C group,while compared with sham group. Simvastatin obviously reduced left ventricle（LV） expansion and improved LV function（P<0.05）.The mRNA expression and protein production of TNF-α markedly increased in MI-C group compared with sham group（P<0.01）,and mRNA expression and protein production of TNF-α markedly lowered in MI-S group compared with MI-C group（P<0.01）.The protein of（TNF-α） mainly located in live myocardial cells of non-infarction and infarction regions,and simvastatin significantly decreased protein production of TNF-α.There existed a positive correlation between mRNA expression of TNF-α and depressed cardiac function.Simvastatin decreased mRNA expression of TNF-α and improved cardiac function. Conclusions Simvastatin may improve ventricular remodeling in rats after MI.The mechanism maybe related to simvastatin-decreasled gene expressionand protein production of TNF-α in non-infarction and infraction region.更多还原