醛固酮致自发性高血压大鼠心肌纤维化的作用机制

MECHANISM OF PATHOGENETIC ROLE OF ALDOSTERONE IN DEVELOPMENT OF MYOCARDIAL FIBROSIS IN SHR

为探索醛固酮介导高血压心肌纤维化作用机制，测定了自发性高血压大鼠（ＳＨＲ）、醛固酮受体拮抗剂螺内酯预处理ＳＨＲ及正常血压大鼠不同培养时间点心肌细胞对３Ｈ－ｐｒｏｌｉｎｅ 掺入量、心肌胶原蛋白含量及丝裂素活化蛋白激酶（ＭＡＰＫ）活性等。结果表明：ＳＨＲ心肌胶原蛋白含量及ＭＡＰＫ活性增加，其各时间点的３ Ｈ－ｐｒｏ－ｌｉｎｅ 摄入量均高于治疗组和正常对照组。说明高血压心肌纤维化可能与醛固酮通过其受体介导心肌ＭＡＰＫ 激活，诱导心肌成纤维细胞对脯氨酸摄入增加而致胶原蛋白合成旺盛有关。

To investigate the mechanism of aldosterone in the induction of hypertensive myocardial fibrosis, we compared the changes of the incorporation rate of 3H proline, the contents of cardiac tissue collagen, and the activities of the cardiac mitogen activated protein kinase (MAPK) in the spontaneous hypertensive rats (SHRs) untreated and treated with a competitive antagonist of the aldosterone receptorspironolactone (spiron), and also in normotensive rats. The results showed that the incorporation of 3H proline incubating with the myocardial tissue slices significantly increased at three time points (at 4,6,8 h), that the tissue collagen contents and the activities of tissue MAPK also increased in SHRs than in SHRs treated with spiron and in normotensive rats. It suggests that aldosterone stimulates the cardiac MAPK through specific recepter, thus increases the absorption of proline and synthesis of collagen in the cardiac fibroblasts, and in turn, is responsible for the myocardial fibrosis.