阿托伐他汀对大鼠心肌梗死后p38磷酸化及心脏重构的影响

Effects of Atorvastatin on p38 Phosphorylation and Cardiac Remodeling after Myocardial Infarction in Rats

目的探究阿托伐他汀对大鼠心肌梗死后p38磷酸化及心脏重构的影响。方法将43只雄性SD大鼠随机分为正常组、假手术组、建模后用药组及建模后非用药组。正常组不做处理,用药组和非用药组结扎冠脉前降支,假手术组在前降支下穿线。正常组进行正常的饲养,用药组大鼠术后每天灌胃阿托伐他汀(10mg/kg),非用药组和假手术组在术后每天灌胃等量的生理盐水。4周后检测各组心功能、心肌细胞形态学改变以及左心室肌TNF-α、p38的表达情况。结果 4周后,非用药组大鼠心肌梗死面积、心肌纤维化、心肌细胞坏死较正常组明显增加,而用药组较非用药组明显减轻(均P<0.05)。非用药组心功能较正常组和假手术组明显下降,而用药组较非用药组心功能明显提升(均P<0.05)。非用药组左心室TNF-α以及磷酸化p38表达量较正常组增加,而用药组较非用药组表达量明显下降(均P<0.05)。结论阿托伐他汀能够改善大鼠心肌梗死后心脏重塑,此作用可能与抑制p38磷酸化,降低TNF-α表达有关。

Objective To explore the effects of atorvastatin on p38 phosphorylation and cardiac remodeling after myocardial infarction in rats.Methods Totally,43 male rats were randomly divided into four groups：normal group,sham group,treatment group and non-drug group.Normal group was not treated;left anterior descending arteries of the rats in the treatment group and non-drug group were ligated.Suture was placed under the left anterior descending arteries of the sham group but not ligated.Rats in the normal group were fed normally.The treatment group was given atorvastatin at 10 mg/kg/day after operation,the non-drug group and sham group were given equal saline.Cardiac function,cell morphology and protein expression were tested four weeks later.Results After four weeks,as compared with the normal group,the infarction area,myocardial fibrosis,cell necrosis in non-drug group were increased（all P〈0.05）.Cardiac function was significantly decreased in the non-drug group as compared with normal group and sham group,but increased in treatment group as compared with the non-drug group（all P〈0.05）.In the non-drug group,the expression levels of phosphorylated p38 and TNF-αwere increased as compared with normal group,but they were less expressed in the treatment group（all P〈0.05）. Conclusion Atorvastatin can improve the cardiac remodeling after myocardial infarction in rats probably through decreasing the expression of TNF-αand inhibiting phosphorylation of p38.