心房纤颤患者心房肌钙激活蛋白酶系统表达变化及意义

Effects of the calpain system expression on atrial structural remodeling in chronic atrial fibrillation

目的探讨慢性心房纤颤患者心房肌钙激活蛋白酶(calpain)系统表达水平改变及其与心房重构的相关性。方法选取进行人工瓣膜置换术的风湿性心脏病房颤患者28例为研究对象,风湿性心脏病窦性心律患者14例为对照组。两组患者术前均进行经胸超声心动图检查,于手术时取左心耳心肌标本,采用荧光实时定量PCR和Westernblot技术检测calpain及其抑制剂calpastatin的mRNA和蛋白的表达量。结果房颤组左心房内径和右心房内径均显著大于对照组(P<0.05～0.001),房颤组和对照组心房肌calpainⅠ、calpainⅡmRNA表达无显著性差异(P>0.05),房颤组calpastatin的mRNA表达明显高于对照组(P<0.05);房颤组calpainⅠ、calpainⅡ蛋白表达明显高于对照组(P<0.05),calpastatin蛋白表达明显低于对照组(P<0.05)。calpainⅠ、calpainⅡ蛋白表达水平与左房内径呈显著正相关(r=0.67,r=0.55,P<0.05),calpastatin蛋白表达水平与左房内径呈显著负相关(r=-0.73,P<0.05)。结论房颤所引起calpain系统的蛋白表达改变,使calpain/calpastatin系统相互间作用失衡,造成多种蛋白被降解可能是心房重构的重要机制。

Objective To evaluate the influence of the calpain system mRNA and protein expression on the progress of atrial structural remodeling in chronic atrial fibrillatoin fatients. Methods Twentyeight patients with chronic atrial fibrillation （AF group） and 14 patients with sinus rhythm （SR, as control group） underwent transthoracic echocardiography and left atrial appendage （LAA） tissue samples were obtained from these patients during mitral/ aortic valve replacement operation. The mRNA and protein expression of calpain Ⅰ , calpain Ⅱ and calpastatin were assessed by real-time quantitative PCR and Western blot respectively. Results Compared with SR group, the left atrial and right atrial diameters increased significantly in AF group （p〈0.05-0.01）. There were no significant differences in mRNA expression of calpain Ⅰ and calpain Ⅱ （P〉0.05） between two groups; the expression of calpastatin mRNA was upregulated significantly in AF group （P〈0.05）. Amounts of calpain Ⅰ and calpain Ⅱ protein were significantly increased in AF group compared with SR group （P〈0.05）; the expression of calpastatin protein was significantly decreased in AF group （P〈0.05）. The calpain Ⅰ and calpain Ⅱ protein levels were positively correlated with the left atrial diameter, the calpastatin protein level was negatively correlated with the left atrial diameter （P〈0.05）. Conclution The changes of the calpain system protein expression in AF can result the disturbance of calpain/calpastatin system and degradation of many proteins, that may represent an important mechanism of atrial remodeling.