The Relationship Of Simvastatin Regulating P38 And CARP With Its Effect Of Reversing Myocardial Remodeling

Objective 1. To investigate the expression mode of p38 mitogen- activated protein kinase (p38MAPK, p38) and Cardiac ankyrin repeat protein (CARP) in rats with myocardial infarction(MI), and its relationship with myocardial remodeling; 2. To investigate the relationship of Simvastatin regulating p38 and CARP with its effect of reversing myocardial remodeling.Methods Twenty-four hours after the induction of MI, the survival rats were randomly assigned to the following groups: MI group(n=25), p38 inhibiter SB203580 group (10μmol/L.kg-1.d-1,n=25, SB group), Sim group (40 mg.kg-1.d -1,n=25) and Sham group (n=15). Each group was further divided into two subgroups of 7, and 28 days. Left ventricular weight index (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 in each group after the hearts being harvested .Results 1. In MI group, serious degeneration and necrosis of cardiomyocytes, inflammatory cells infiltration, great acceleration of collagen were observed in infarcted area, and compensatory hypertrophy of cardiomyocytes were observed in noninfarcted area; cytolysis, augmentation of chondrosome in cardiomyocytes and obvious myofilamentlysis at contraction bands were found in electron microscope. In SB group pathological changes was lighter, and the lightest in Sim group compared with MI group. 2. Compared with Sham group, LVWI and CSA significantly increased in MI group (P<0.05); there were no statistical difference of the expression of p38 mRNA in MI group (P>0.05), but the expression of p-p38 significantly elevated (P<0.05); CARP mRNA and protein increased in 7d MI subgroups (P<0.05). Compared with MI group, LVWI and CSA significantly decreased in Sim group (P <0.05); the expression of p38 mRNA, CARP mRNA, p-p38 and CARP protein abated in 7d Sim subgroups (P<0.01). Compared with MI group, LVWI of SB group decreased in 7d subgroup (P<0.01), and CSA decreased in both 7d and 28d SB subgroups (P<0.01); the expression of p38 mRNA increased in 28d SB subgroup, and CARP mRNA decreased in 7d SB subgroup (P<0.01). Compared with Sim group, the expression of p38 mRNA was higher in SB group, and p-p38 higher in 7d SB subgroup (P<0.01).Conclusion1. p38 and CARP are upregulated in rats with MI;2. The inhibition of p38 can downregulate CARP, and CARP is probably regulated partly by p38 signaling pathway;3. The effect of simvastatin reversing myocardial remodeling is fulfilled, at least partly, through downregulating p38 and CARP.