钙激活蛋白酶系统与慢性房颤犬心房重构关系的研究

目的： 探讨慢性房颤犬心房肌钙激活蛋白酶（calpain）系统表达水平的改变及其与心房重构的相关性。方法： 17只杂种犬随机分为心房颤动组（11只）和对照组（6只），于起搏前后均进行经胸超声心动图检查，测量舒张期左房内径。房颤组经颈外静脉将电极置入右心耳快速起搏（400 beats/min）8周复制房颤模型，开胸取心房组织，测定心房肌Ca2+浓度，用荧光实时定量PCR和Western blotting技术检测calpain及其抑制剂calpastatin mRNA和蛋白的表达量。结果： 房颤组心房肌Ca2+浓度升高，左房内径显著大于起搏前及对照组(P<0.05)，房颤组和对照组比较犬心房肌calpainⅠ、calpainⅡmRNA表达无显著差异(P＞0.05)，房颤组calpastatin 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=0.53，r=0.67,P<0.05)，calpastatin蛋白表达水平与左房内径呈显著负相关(r=-0.74，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。

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

AIM: To evaluate the influence of the calpain system mRNA and protein expression on the progress of atrial structural remodeling in fibrillating canine.METHODS: 17 dogs were randomly divided into 2 groups: normal control group (SR,n=6) and atrial fibrillation (AF,n=11) group.AF was induced by rapid pacing for 8 weeks and all dogs underwent transthoratic echocardiography before and after rapid pacing.The mRNA and protein expression of calpainⅠ,calpainⅡand calpastatin were assessed by real-time quantitative PCR and Western blotting,respectively.RESULTS: Compared with SR group,the left atrial diameters and the content of calcium in atrial myocardium increased significantly in AF group (P<0.05).There was no significant difference in mRNA expression of calpainⅠand calpainⅡ (P>0.05) between two groups.The expression of calpastatin mRNA was upregulated significantly in AF group (P<0.05).The levels of calpainⅠand calpainⅡprotein 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 calpainⅠand calpainⅡprotein levels were positively correlated with the left atrial diameter.The calpastatin protein level was negatively correlated with the left atrial diameter (P<0.05).CONCLUSION: The changes of the calpain system protein expression in AF result in the disturbance of calpain/calpastatin system and degradation of many proteins,which may play an important role in mechanism of atrial remodeling.