辛伐他汀对心肌梗死后心肌骨桥蛋白表达的影响及其与心室功能的相关性

Effect of simvastatin on osteopontin expression and its correlation with ventricular remodeling in rats after myocardial infarction

目的在大鼠心肌梗死模型上,观察辛伐他汀是否下调OPN mRNA及蛋白表达,及其与改善大鼠心肌梗死后心室重塑和心脏功能的关系。方法制备MI模型,予辛伐他汀干预。分为3组:Sim组、MI组及假手术组。4周后分别测定左、右心室质量指数,血流动力学指标,HE染色观察心肌组织病理学改变,运用免疫组化、RT-PCR方法检测OPN蛋白及mRNA表达并与假手术组比较。结果 MI组较Sham组左、右心室质量指数均有所增加(P<0.01),血流动力学变化(P<0.01),心肌中OPN mRNA及蛋白表达量明显增加(P<0.01);Sim组较MI组左、右心室质量指数均有下降(P<0.01),血流动力学改善(P<0.01),心肌中OPN mRNA及蛋白表达量明显降低(P<0.01);MI组OPN mRNA表达与左、右心室质量指数呈显著正相关(r=0.760,P=0.029;r=0.804,P=0.016),与LVEF、FS变化呈显著负相关(r=-0.791,P=0.020;r=-0.841,P=0.009)。结论辛伐他汀改善MI后左心室重塑和心功能,这可能与其在基因转录和蛋白质翻译水平抑制OPN表达等综合因素有关。

Objective To investigate the effect of simvastatin on mRNA and protein expression of osteopontin（OPN） and simvastatin association with improvement of cardiac remodeling and cardiac function in rat model of myocardial infarction（MI）.Methods Rat MI models were constructed in Wistar rats.There were three groups： a Sim group [Simvastatin 40mg/（kg·d）],an MI group [normal saline 40 mg/（kg·d）] and a Sham group [normal saline 40 mg/（kg·d）].After four weeks treatment,indices of ventricular weight and hemodynamics were measured,pathological changes of cardiac muscular tissues were observed by HE staining,and mRNA and protein expression of OPN in cardiac muscles were measured by immunohistochemistry and RT-PCR.Results Compared with those in the Sham group,the indices of ventricular weight and hemodynamics and mRNA and protein expression of OPN in the MI group increased significantly（P〈0.01）.Compared with the MI group,indices of ventricular weight and hemodynamics and mRNA and protein expression of OPN in the Sim group decreased significantly（P〈0.01）.In the MI group,OPN mRNA expression positively correlated with ventricular weight index（r=0.760,P=0.029;r=0.804,P=0.016）,and negatively correlated with echocardiogram indices（LVEF,FS）（r=-0.791,P=0.020;r=-0.841,P=0.009）.Conclusion Simvastatin can effectively improve ventricular remodeling and cardiac function in rats with MI.The mechanism may be related to the inhibitory effect of simvastatin on mRNA and protein expression of OPN.