目的观察风湿性心脏瓣膜病合并房颤患者右心房组织中转化生长因子β1(TGF-β1)及Smad3的表达变化,探讨TGF-β1信号通路在房颤心房结构重构中的意义。方法 2009年10月-2010年5月40例接受单纯二尖瓣置换术的风心病患者,根据病史和术前心电图记录分为慢性房颤组(AF组,n=28)和窦性心律组(SR组,n=12)。术前心脏彩超测定各心腔大小并评价心功能。术中取右心房组织,行Masson及天狼猩红苦味酸染色,观察纤维化情况并计算胶原容积分数(CVF),采用实时荧光定量PCR和West-ern blotting检测右心房组织中TGF-β1、Smad3的mRNA及蛋白表达情况。结果与SR组相比,AF组右心房组织胶原纤维增生明显,TGF-β1、Smad3mRNA及蛋白表达均显著增高(P〈0.05)。AF组中右心房组织TGF-β1 mRNA及蛋白表达水平均与胶原容积分数呈正相关,相关系数r分别为0.584(P=0.010)和0.671(P=0.024)。AF组TGF-β1与Smad3的表达在mRNA及蛋白水平均呈正相关(r=0.634,P=0.020;r=0.757,P=0.003)。结论房颤时发生以心房纤维化改变为主的心房结构重构;TGF-β1/Smad途径可能参与了房颤患者心房结构重构进程,与房颤的发生和维持有关。
Objective To observe the expressions of transforming growth factor beta 1(TGF-β1) and mothers against decapentaplegic homolog 3(Smad3) in the right atrium of patients with rheumatic heart valve disease(RHVD) and discuss the roles of the TGF-β1 signal pathway in the structural remodeling of atrial fibrillation(AF).Methods Up to 40 cases of rheumatic heart valve disease that underwent mitral valve replacements from Oct 2009 to May 2010 were selected in the present study.The patients were divided into 2 groups: sinus rhythm(SR) group(n=12) and chronic atrial fibrillation(AF) group(n=28) based on their history and electrocardiogram reports before surgery.Echocardiography was used to measure the cardiac cavity size,and analyze cardiac function.Right atrial specimens were obtained during the operation for Masson and Sirius red picric acid staining and to observe fibrosis and calculate the collagenous volumetric fraction(CVF).TGF-β1,Smad3 mRNA and protein expression were measured via real-time quantitative polymerase chain reaction and Western blot.Results Compared with the SR group,the AF group had a higher collagen in the right atrial myocardium.The expression levels of TGF-β1,Smad3 mRNA,and protein were significantly increased(P〈0.05).In the AF group,the TGF-β1 mRNA and protein expression levels in the right atrial myocardium were positively correlated with the CVF with a relationship index r=0.584 for(P=0.010)and 0.671 for(P=0.024),respectively.The expression levels of TGF-β1 and Smad3 were positively correlated with the mRNA and protein levels(r=0.634,P=0.020;r=0.757,P=0.003).Conclusions An structural remodeling of the atria based mainly on the change of atrial fibrosis will occur during atrial fibrillation.TGF-β1/Smad3 may play a part in the atrial structural remodeling of AF patients,and it is related to the occurrence and maintenance of atrial fibrillation.