microRNA-133对终末期扩张型心肌病心肌纤维化调控的作用  

Effects of microRNA-133 on end-stage myocardial fibrosis of dilated cardiomyopathy

作　　者：王勇[1] 厉泉[2] 陈善良[2] 王东[2] 于建民[2] 李敏[2] 刘天起[2] 

机构地区：[1]潍坊医学院,山东潍坊261053 [2]山东大学附属千佛山医院心外科,山东省心脏移植与材料工程技术研究中心,山东济南250014

出　　处：《山东大学学报（医学版）》2015年第5期60-65,共6页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金(Z2006C10)

摘　　要：目的探讨microRNA-133(miR-133)在扩张型心肌病(DCM)心肌纤维化过程中的作用。方法收集行心脏移植的DCM患者心肌组织标本21例(DCM组),意外创伤性脑死亡而无心脏疾病患者心肌组织标本10例(对照组)。Masson染色观察心肌纤维化状况,原位末端标记法(TUNEL法)观察心肌细胞凋亡情况。培养人心肌成纤维细胞,转染miR-133模拟物(miR-133a mimic、miR-133b mimic),上调心肌成纤维细胞miR-133(miR-133a、miR-133b)的表达,应用RT-PCR法检测miR-133a、miR-133b的表达,应用RT-PCR、Western boltting法分别检测BCL-2 mRNA和蛋白水平表达。结果 DCM组心肌组织中出现严重的心肌纤维化和心肌细胞凋亡,左、右心室心肌间质和血管周围胶原(CVF)增多(P<0.01);凋亡指数增高(P<0.05);细胞凋亡相关蛋白BCL-2表达上调(P<0.05);人心肌成纤维细胞转染miR-133a mimic、miR-133b mimic后,miR-133a、miR-133b表达上调(P<0.01),BCL-2表达显著下降(P<0.01)。结论 DCM心肌组织中miR-133能够减弱BCL-2对心肌成纤维细胞的诱导,抑制心肌成纤维细胞病理增生,减轻DCM心肌纤维化。Objective To investigate the effects of microRNA-133 （miR-133） on myocardial fibrosis of dilated cardio- myopathy （DCM）. Methods A total of 21 myocardial samples of DCM patients undergoing cardiac transplantation （DCM group） and 10 myocardial samples of brain-dead victims of accidental trauma who had no medical evidence of cardiac disease （ control group） were collected. The degrees of myocardial fibrosis were observed with masson staining, and cardiomyocyte apoptosis was determined with TdT-mediated dUTP Nick-End Labeling （TUNEL）. Human cardiac fibroblasts were cultured, and miR-133mimic（ miR-133a mimic and miR-133b mimic） was transfected into the fibro- blasts to investigate the effects of miR-133（miR-133a and miR-133b） on myocardial fibrosis. The mRNA expressions of BCL-2 and miR-133 were detected with RT-PCR, and the protein expression of BCL-2 was evaluated with Western blotting. Results In DCM group, severe myocardial fibrosis and myocardial cell apoptosis were observed, collagen volume fraction （CVF） was increased （left ventricle P 〈0.01 ; right ventricle P 〈0.01 ）, myocardial apoptosis index was higher （ left ventricle P 〈 0.05 ; right ventricle P 〈 0.05 ）, and apoptosis-related protein BCL-2 was increased （ P 〈 0.05 ; right ventricle P 〈 0.05 ）. After miR-133a mimic and miR-133b mimic were transfected into human cardiacfibroblasts, the expression of miR-133a and miR-133b were elevated （P 〈0.01 ） and BCL-2 was decreased （P 〈0.01 ）. Conclusion In myocardial tissues of DCM patients, miR-133 can attenuate the stimulation on cardiac fibroblasts induced by BCL-2, inhibit pathologic proliferation of myocardial fibroblasts, and reduce myocardial fibrosis of DCM.

关 键 词：扩张型心肌病 心肌纤维化 microRNA-133 BCL-2 

分 类 号：R542.2[医药卫生—心血管疾病]