辛伐他汀调节p38和CARP与改善心肌重塑的关系

 目的探讨p38丝裂原激活的蛋白激酶(p38MAPK,p38)和心锚重复蛋白(cardiac ankyrin repeat protein,CARP)与心肌梗死后心肌重塑的关系,及辛伐他汀改善心肌梗死后心肌重塑的机制。方法结扎大鼠冠脉前降支致心肌梗死,术后24h存活大鼠随机分为心肌梗死组(MI组)、p38抑制剂SB203580组(SB组)、辛伐他汀组(Sim组)和假手术组(sham组)。7d后测定左心室重量指数(LVWI),心肌细胞横切面面积(CSA),RT-PCR和免疫组化法测定p38和CARP在非梗死区心肌中的表达。结果与Sham组相比,MI组LVWI和CSA明显增加(P<0.01),磷酸化p38(P-p38)和CARP表达明显增加(P<0.05)。与MI组相比,SB组和Sim组LVWI和CSA明显降低(P<0.01),SB组CARP表达低于MI组(P<0.01),Sim组p38和CARP表达明显低于MI组(P<0.01)。结论大鼠心肌梗死后p38和CARP表达增加;抑制p38可抑制CARP的表达,CARP可能部分受p38信号通路调节;辛伐他汀改善心肌梗死后心肌重塑的作用可能与抑制p38和CARP有关。

Inhibition of Simvastatin on p38 and CARP and Its Improving Effect on Myocardial Remodeling

OBJECTIVE To investigate the role of p38 mitogen-activated protein kinase(p38MAPK,p38) and cardiac ankyrin repeat protein(CARP) in myocardial remodeling in rats with myocardial infarction(MI),and the mechanism of simvastatin(Sim) improving myocardial remodeling after MI.METHODS After the induction of MI for 24 h,the survival rats were randomly assigned to MI group,p38 inhibiter SB203580 group(SB group),Sim group and Sham group.After 7 d,left ventricular weight(LVWI),cardiomyocyte cross-sectional area(CSA) and the expression of p38 and CARP in noninfarcted region of hearts were measured by RT-PCR and immunohistochemistry.RESULTS Compared with Sham group,LVWI and CSA of MI group were significantly increased(P<0.01).There was no great change of the expression of p38 in MI group at mRNA level(P>0.05),but a great upregulation was observed at P-p38 protein level(P<0.05),and the expression of CARP was elevated both at mRNA and protein level(P<0.05).Compared with MI group,LVWI and CSA were decreased in SB group and Sim group;the expression of CARP mRNA was greatly downregulated in SB group(P>0.05);in Sim group,the expression of p38 and CARP were lower than those in MI group both at mRNA and protein level(P<0.01),and also were lower than those in SB group(P<0.01).CONCLUSION p38 and CARP are upregulated in rats with MI.The inhibition of p38 can downregulate CARP,and CARP is probably regulated partly by p38 signaling pathway.The effect of simvastatin improving myocardial remodeling in rats with MI was related to,at least partly,downregulating p38 and CARP.