p38和CARP的表达与大鼠心肌梗死后心肌重塑的关系

Relationship between the expressions of p38 and CARP and myocardial remodeling in rats with myocardial infarction

目的探讨p38丝裂原激活的蛋白激酶(p38)和心锚重复蛋白(CARP)的表达与大鼠心肌梗死(MI)后心肌重塑的关系。方法结扎大鼠冠脉前降支致MI,术后2 h存活大鼠随机分为MI组、p38抑制剂SB203580组(SB组)和假手术组(Sham组)。测定各组第1、7和28天左心室质量指数(LVWI)、心肌细胞横切面面积(CSA)。RT-PCR法测定p38和CARP在心脏的表达。结果与Sham组相比,MI组LVWI和CSA在第7、28天时明显增加(P均<0.05),各时间点磷酸化p38(p-p38)表达均明显升高(P均<0.05),CARP在第1、7天时表达明显升高(P均<0.05)。与MI组相比,SB组LVWI在第7天时明显降低(P<0.01);CSA在第1天时增大(P<0.01),第7、28天时明显缩小(P均<0.01);p-p38在第1天时表达降低,CARP在第7天表达降低(P<0.01)。结论MI后早期p38和CARP即被激活,并促进随后心肌重塑的发展,抑制p38可以抑制CARP,改善心肌重塑。

Objective To investigate the relationship of p38 mitogen-activated protein kinase（p38） and cardiac ankyrin repeat protein（CARP） with myocardial remodeling in rats with myocardial infarction（MI）.Methods MI of rats was induced by ligating anterior descending coronary.Two hours after the induction of MI,the survival rats were randomly assigned to MI group,p38 inhibiter SB203580 group（SB group）,and sham operated group（Sham group）.Left ventricular weight index（LVWI） and cardiomyocyte cross-sectional area（CSA） in all groups were detected on 1st, 7th , 28th day.The expressions of p38 and CARP in noninfarcted myocardium were measured by RT-PCR and immunohistochemistry in each group. Results Compared with Sham group, LVWI and CSA increased on 7th and 28th day in MI subgroups （ P 〈 0.05）, the expression of phosphorylated p38 （ p-p38 ） elevated in all MI subgroups in all time points （ all P 〈 0.05 ） ; CARP increased on 1st and 7th day （P 〈0.05）. Compared with MI group, in SB subgroup, LVWI decreased on 7th day （ P 〈 0.01 ）, and CSA increased on first day, decreased on 7th and 28th day（ P 〈 0.01 ） ; the expression of p-p38 lowered on the first day（ P 〈 0.01 ） , and CARP mRNA decreased on 7th day（ P 〈 0.01 ）. Conclusions p38 and CARP are activated in rats with MI at early time, and subsequently promote myocardial remodeling. The inhibition of p38 leads to the downregrlation of CARP and the improvement of myocardial remodeling.