转化生长因子β_1促风湿性心脏病心肌细胞胶原合成的调控机制  

The regulatory mechanisms of collagen synthesis induced by transforminggrowth factor beta-1 in cardiomyocytes with rheumatic heart disease

作　　者：宋智钢[1] 刘维永[1] 蔡振杰[1] 俞世强[1] 张近宝[1] 胡巧霞[1] 

机构地区：[1]第四军医大学西京医院心血管外科中心

出　　处：《临床心血管病杂志》2004年第2期65-68,共4页Journal of Clinical Cardiology

基　　金：国家自然科学基金资助项目 (No :39870 790 )

摘　　要：目的 :揭示转化生长因子 β1(TGF β1)促风湿性心脏病 (风心病 )心肌细胞胶原合成的信号转导机制。方法 :应用风心病患者心肌细胞体外培养模型 ,反转录 聚合酶链反应和Western蛋白印迹方法检测不同浓度人TGF β1( 5、10、2 0 μg/L)刺激风心病患者心肌细胞Ⅰ、Ⅲ型前胶原mRNA、Ⅰ型胶原蛋白、c fos、c jun和磷酸化c jun (Phospho c jun)的表达情况 ;以及蛋白激酶C(PKC)拮抗剂Staurosporine(SP)预处理对其作用的影响。结果 :人TGF β1呈浓度依赖性的方式促进风心病患者心肌细胞Ⅰ、Ⅲ型前胶原mRNA、Ⅰ型胶原蛋白以及c fos、c jun、Phospho c jun的表达 ;SP预处理不仅抑制其表达 ,同时部分逆转人TGF β1上调胶原基因和蛋白表达的效应。结论 :TGF β1通过介导PKC的活化 ,激活核转录因子AP 1。Objective: To investigate the intracellular signal transduction mechanisms of collagen synthesis induced by transforming growth factor beta 1 (TGF β 1) in rheumatic cardiomyocytes. Methods: The adult cardiomyocytes from patients with rheumatic heart disease were cultured in vitro. The cardiomyocytes cultured in vitro were stimulated by different concentration of human TGF β 1(5, 10, 20 μg/L). RT PCR and Western Blotting were used to examine the expression of typeⅠ/Ⅲ procollagen mRNA, the protein quantity of typeⅠcollagen, c fos, c jun and Phospho c jun in rheumatic cardiomyocytes induced by human TGF β 1, and pretreated with Staurosporine during TGF β 1 stimulation. Results: Human TGF β 1 could enhance the expression of typeⅠ/Ⅲ procollagen mRNA, typeⅠcollagen, c fos, c jun and Phospho c jun in a dose dependent manner. Pretreatment of rheumatic cardiomyocytes with Staurosporine, which are specific inhibitors of protein kinase C, could partly block the expression of c fos, c jun and Phospho c jun and reverse the expression of typeⅠ/Ⅲ procollagen mRNA and typeⅠcollagen at the same time. Conclusion: TGF β 1 can activate nuclear transcription factor AP 1 by mediating the activation of protein kinase C. These signal transducers take part in intracellular signal transduction pathways of collagen synthesis induced by TGF-β 1 in rheumatic cardiomyocytes.

关 键 词：风湿性心脏病 心肌 胶原 转化生长因子Β 信号转导 

分 类 号：R542.2[医药卫生—心血管疾病]