辛伐他汀对心肌梗死大鼠心室重构的影响

Effect of simvastatin on ventricular remodeling in rats after myocardial infarction

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。

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 - deereasled gene expression and protein production of TNF-α in non-infarction and infraction region.