风湿性心脏病心房颤动患者心房肌TGF-β1信号通路表达改变的研究  

Expression changes in TGF-β1 signal pathway in atrial myocardium of patients with rheumatic heart disease and atrial fibrillation

作　　者：史航[1] 李荣淼[2] 姜永日[3] 樊占威 陈伟光[3] 宋巍 王四清 王柏春[3] Shi Hang;Li Rongmiao;Jiang Yongri;Fan Zhanwei;Chen Weiguang;Song Wei;Wang Siqing;Wang Baichun(Department of Cardiovascular Surgery,the First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学附属第一医院心血管外科,150001 [2]桓台县人民医院胸外科,淄博256400 [3]哈尔滨医科大学附属第四医院心血管外科,150001

出　　处：《国际遗传学杂志》2018年第5期323-329,共7页International Journal of Genetics

基　　金：黑龙江省自然科学基金（D201117）;黑龙江省普通高等学校医学遗传学重点实验室开放基金

摘　　要：目的研究风湿性心脏病心房颤动患者心房肌TGF-β1信号通路表达情况，揭示TGF-β1信号通路在心房颤动演变过程的作用机制。方法组织样本采自于90例开胸风心病瓣膜置换术患者，其中心房颤动组50例，窦性心律组40例。应用Realtime-PCR和蛋白质印迹方法检验TGF-β信号传导通路中各信号因子的mRNA和蛋白表达水平，包括：非smad信号通路中ERK1/2、JNK和P38；Rac1信号通路中Rac1、connexin 43和N-cadherin，并分析上述6种蛋白与Ⅰ型胶原蛋白的关系。结果Realtime-PCR结果显示与窦律组比较，在房颤组中ERK1/2（P＝0.007）、P38（P＝0.028）、connexin 43（P＝0.040）和N-cadherin（P＝0.003） mRNA表达上调。JNK（P＝0.210）、Rac1（P＝0.463）房颤组与窦律组比较无明显差异，没有统计学意义。Western印记显示与窦律组比较，在房颤组中ColⅠ（P〈0.001）、ERK1/2（P＝0.015）、P38（P＝0.013）、connexin 43（P＝0.036）和N-cadherin（P＝0.003）蛋白表达上调。JNK（P＝0.081）、Rac1（P＝0.753）房颤组与窦律组比较无明显差异。其结果和mRNA表达一致。另外，通过相关性分析发现6种检测因子的蛋白表达均与ColⅠ蛋白表达存在正相关。相关系数分别为（0.578、0.353、0.568、0.345、0.488、0.490），P值分别为（0.009、0.024、0.015、0.038、0.036、0.044）。结论在风心病房颤的心房中存在明显的Ⅰ型胶原纤维堆积，可能与心房颤动的发生密切相关。风湿性心脏病心房颤动患者心房肌中TGF-β1下游信号分子ERK1/2、P38、connexin 43和N-cadherin存在过表达，可能与风湿性心脏病心房颤动的发生、发展有关。6种目的蛋白均与ColⅠ蛋白存在正相关关系，可能与风心病心房纤维化、心肌胶原增多有关。ObjectiveStudy on expression changes in TGF-β1 signal pathway in atrial myocardium of patients with rheumatic heart disease and atrial fibrillation （AF）, to reveal the underlying mechanism of TGF-β1 signaling pathway downstream signal molecules in atrial fibrillation evolution.MethodsAtrial tissue samples from 90 patients undergoing open-heart surgery were collected. Fifty patients had rheumatic heart disease and chronic persistent AF, and 40 patients had rheumatic heart disease but sinus rhythm. We detected the expression level of mRNA and protein of the signal factors in the TGF-β signaling pathway by real-time quantitative PCR and Western blot.ResultsRealtime-PCR results showed that compared with sinus rhythm group, the expression of ERK1/2 （P=0.007）, P38 （P=0.028）, connexin 43 （P=0.040） and N-cadherin （P=0.003） mRNA were up-regulated in AF group. JNK （P=0.210）, Rac1 （P=0.463） atrial fibrillation group and sinus rhythm group had no significant difference. Western blot showed that the expression of ColⅠ （P〈0.001）, ERK1/2 （P=0.015）, P38 （P=0.013）, connexin 43 （P=0.036） and N-cadherin （P=0.003） were up-regulated in AF group compared with sinus rhythm group. JNK （P=0.081）, Rac1 （P=0.753） atrial fibrillation group and sinus rhythm group were not significantly different. The results are consistent with mRNA expression. In addition, correlation analysis showed that the expression of the six detection factors were positively correlated with the expression of ColⅠ protein. The correlation coefficients were （0.578, 0.353, 0.568, 0.345, 0.488, 0.490） and P values were （0.009, 0.024, 0.015, 0.038, 0.036, 0.044）, respectively.ConclusionCollagen Ⅰ fibers obviously accumulate in atrial tissue among those with rheumatic AF, which may correlate with the occurrence of AF. Overexpression of ERK1/2, P38 in non-Smad signal pathway and connexin 43. N-cadherin in CTGF downstream signal molecules in atria of patients with rheumatic heart disease and AF may be

关 键 词：风湿性心脏病 心房颤动 心房纤维化 TGF-β1信号通路 

分 类 号：R541.2[医药卫生—心血管疾病] R541.75[医药卫生—内科学]