心肌重塑中AT_1受体β_1受体与PKC和MAPKs信号转导通路间关系的探讨

Correlation of cardiac AT_1 receptor and β_1 receptor with PKC/MAPKs signal transduction pathway in myocardial remodeling.

目的 探讨心肌重塑中AT1受体、β1受体与PKC和MAPKs信号转导通路间的关系 ,以进一步探讨心肌重塑的分子机制。方法 Wistar大鼠 2 4只 ,随机分为 4组 ,分别为假手术组、单纯心肌梗死组、氯沙坦组和倍他乐克组 ,结扎左冠状动脉前降支建立大鼠心肌梗死后心肌重塑模型 ,均观察 2 1d ,其中假手术组不结扎冠状动脉。心肌I型、III型胶原、纤维连接蛋白、c fos、细胞外信号调节激酶 (ERK)和蛋白激酶C(PKC)表达的变化均用免疫组织化学染色法和计算机图像分析进行检测分析。用RT PCR方法检测c fos受体mRNA表达的变化。结果 单纯梗死组心肌I型、III型胶原、纤维连接蛋白 (FN)、c fos、ERK1和PKC蛋白表达增强 ,与假手术组比较均有显著性差异 (P <0 0 5或P <0 0 1) ,且c fosmRNA表达增强 ;氯沙坦组心肌Ⅰ型、Ⅲ型胶原、FN、c fos、ERK1和PKC蛋白表达均比单纯梗死组显著减少 (P <0 0 5或P <0 0 1) ,c fosmRNA表达减弱 ,而倍他乐克组对PKC和ERK1表达无明显影响。结论 PKC和MAPK信号转导通路与心肌梗死后心肌重塑相关 ,其中心脏AT1受体与PKC和MAPK信号转导通路有关 ,而 β1受体与PKC和MAPK信号转导通路可能无关 。

Objective To inquire into the correlation of cardiac AT 1 receptor,β 1 receptor with PKC/MAPKs(protein kinase C/mitogen-activated protein kinase) signal transduction pathway during myocardial remodeling.Methods Twenty-four Wistar rats were randomly divided into four groups-sham group,infarcted group,losartan group and betaloc group.Except sham group,left anterior descending coronary artery was ligated for 21 days.In the other three groups,expression changes of cardiac collagen subtype Ⅰ,Ⅲ,fibronectin(FN),c-fos,ERK 1 (extracellular signal-regulated kinase,ERK)and PKC proteins were studied with immunohistochemistry and computer image analysis. c-fos mRNA expression was tested by reverse transcription and polymerase chain reaction(RT-PCR).Results Expressions of collagen Ⅰ,collagen Ⅲ , FN,c-fos,ERK 1 and PKC proteins were significantly enhanced(P<0.05 or P<0.01) in infarcted group compared with those in sham group,and c-fos mRNA expression was inceased. In losartan group,cardiac collagenⅠ,collagen Ⅲ,FN,c-fos,ERK 1 and PKC protein expressions were remarkably decreased than in infarcted group (P<0.05 or P<0.01);but in betaloc group, ERK 1 and PKC protein expressions were not affected.Conclusion PKC/MAPK signal transduction pathway relates to myocardial remodeling after myocardial infarction;cardiac AT 1 receptor correlates with PKC/MAPK signal pathway,but β 1-adrenergic receptor is not associated with PKC/MAPK signal pathway.Cardiac β 1-adrenergic receptor may affect myocardial remodeling through other signal pathways,which needs further study.