风湿性心脏病合并持续性心房颤动患者左心房内径增大对心房肌组织Ang Ⅱ/Rac1/STAT3途径表达的影响

Effect of left atrial enlargement on expression of the angiotensin Ⅱ, signal transducers and activators of transcription 3 and Rac GTPase activating protein 1 signaling pathways in patients with persistent atrial fibrillation and rheumatic heart disease

目的探讨风湿性心脏病合并持续性心房颤动(房颤)患者左心房内径增大对心房肌组织纤维化程度以及血管紧张素Ⅱ(AngⅡ)/Rac GTP酶激活蛋白1(Rac1)/信号转导与转录激活因子3(STAT3)信号途径表达水平的影响。方法选取2011年3～12月30例在我院行人工瓣膜置换术的风湿性心脏病患者,其中男16例、女14例,年龄42～70(56.9±6.8)岁。将10例窦性心律患者为作对照组(A组);合并持续性房颤20例患者为病例组,按左心房内径(LAD)分为两组,B组LAD 50～65 mm(n=10),C组LAD>65 mm (n=10)。术中建立体外循环后获取右心耳组织标本,采用HE及Masson染色,并辅以显微图像分析软件计算组织纤维化程度。酶联免疫吸附试验检测心房肌组织的AngⅡ浓度和蛋白印迹法检测心房肌组织Rac1、STAT3蛋白的表达。结果房颤患者左心房内径与对照组比较明显增大。随着左房内径增加,HE染色显示心肌细胞体积增大、数量减少,同时心肌细胞排列紊乱加重及细胞核大小不均一。此外Masson染色显示心房肌细胞周围胶原纤维沉积明显增加并分割包绕。心房肌组织中AngⅡ浓度、Rac1与STAT3蛋白表达水平随左心房内径增大表达水平增强,并与左心房内径呈正相关。结论风湿性心脏病合并持续性房颤患者,心房肌组织纤维化程度以及AngⅡ/Rac1/STAT3信号途径表达水平随左心房内径增大明显增强。

Objective To evaluate the effect of left atrial enlargement on atrial myocardial fibrosis degree and levels of the angiotensinⅡ（AngⅡ）/Rac GTPase activating protein 1（Rac1）/signal transducers and activators of transcription 3（STAT3） signaling pathways expressing in patients with persistent atrial fibrillation and rheumatic heart disease（RHD）. Methods From March to December 2011, 30 patients with RHD who underwent prosthetic valve replacement in our hospital were enrolled, including 16 males and 14 females, aged 42-70（56.9±6.8） years. Twenty RHD patients with persistent atrial fibrillation as a research group and ten RHD patients with sinus rhythm as a control group（group A） underwent transthoracic echocardiography and right atrial appendage（RAA） tissue samples were obtained from these patients during mitral/aortic valve replacement operation. The research group according to left atrial diameter（LAD） was divided into two groups, ten patients in each group： a group B with LAD of 50–65 mm and a group C with LAD of LAD65 mm. For each sample, histological examination was performed by hematoxylin-eosin and Masson＇s trichrome staining. Light-microscopic pictures of atrial tissues samples were stained and tissue fibrosis degree in each group was analyzed. AngⅡ concentration was measured by enzyme linked immunosorbent assay. Rac1 and STAT3 were measured by western blotting. Results LAD was significantly greater in AF patients with RHD than in the control group. Hematoxylin-eosin staining demonstrated highly organized arrangement of atrial muscles in the control group and significant derangement in both group B and group C with reduced cell density and increased cell size. Moreover, Masson＇s trichrome staining showed that atrial myocytes were surrounded by large trunks of collagen fibers in both group B and group C, but not in the group A. There was a positive correlation between atrial tissue fibrosis and LAD. AngⅡ content was positively correlated with LAD. Similarly, Rac1 and STAT3 protein levels were found considerably higher in the group C and group B than in the group A with excellent correlation to LAD.Conclusion In patients with RHD complicated with persistent atrial fibrillation, the degree of atrial fibrosis and the expression level of AngⅡ/Rac1/STAT3 signaling pathways significantly increase with the left atrial enlargement.