【作者】 李向东；

【导师】 覃数；

【作者基本信息】 重庆医科大学 ， 内科学， 2008， 硕士

【摘要】 目的:1.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)在大鼠心肌梗死(MI)后的表达变化,及其与MI后心肌重塑的关系;2.探讨辛伐他汀改善心肌重塑的作用是否与p38和CARP有关。方法:结扎大鼠冠脉前降支致MI,术后24h存活大鼠随机分为MI组(n=25)、p38抑制剂SB203580组(SB组,10μmol/L.kg -1.d -1,n=25)、辛伐他汀组(Sim组,40 mg.kg -1.d -1,n=25)和假手术组(Sham组,n=15)。再将上述各组分为7d和28d二个亚组。各组均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在心脏的表达。结果:1. MI组大鼠梗死区心肌细胞严重变性坏死,炎性细胞浸润,大量胶原纤维增生,非梗死区心肌细胞出现代偿性增生肥大;电镜显示,梗死交界区细胞溶解,线粒体明显增多,肌节中断,有明显收缩带肌丝溶解。SB组大鼠病变较轻,Sim组大鼠病变最轻。2. MI组与Sham组相比,前者LVWI和CSA明显增高(P<0.05),p38 mRNA表达无明显改变(P>0.05),但磷酸化p38(p-p38)表达明显升高(P<0.05),CARP mRNA和蛋白在7d时表达升高(P<0.05)。Sim组与MI组相比,前者LVWI和CSA明显降低(P<0.05),p38 mRNA、CARP mRNA、p-p38和CARP蛋白在7d时表达明显降低(P<0.01)。SB组与MI组相比,前者LVWI在7d时明显降低(P<0.01),CSA在7d和28d时均明显减小(P<0.01),p38 mRNA在28d时表达升高,CARP mRNA在7d时表达降低(P<0.01)。SB组与Sim组相比,前者p38 mRNA表达增高(P<0.01),p-p38表达在7d时高于Sim组(P<0.01),CARP表达两组间比较无明显差异(P>0.05)。结论:1.大鼠心肌梗死后p38和CARP表达增加;2.抑制p38可抑制CARP的表达,CARP可能部分受p38信号通路调节;3.辛伐他汀改善MI后心肌重塑的作用可能与抑制p38和CARP有关。更多还原

【Abstract】 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.更多还原