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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (5): 60-65.doi: 10.6040/j.issn.1671-7554.0.2015.039

• 临床医学 • 上一篇    下一篇

microRNA-133对终末期扩张型心肌病心肌纤维化调控的作用

王勇1, 厉泉2, 陈善良2, 王东2, 于建民2, 李敏2, 刘天起2   

  1. 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
  • 收稿日期:2015-01-12 修回日期:2015-03-20 出版日期:2015-05-10 发布日期:2015-05-10
  • 通讯作者: 刘天起。E-mail:tianqiliu12@aliyun.com;李敏。E-mail:liminzijia1210@126.com E-mail:tianqiliu12@aliyun.com;liminzijia1210@126.com
  • 基金资助:
    山东省自然科学基金(Z2006C10)

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

WANG Yong1, LI Quan2, CHEN Shanliang2, WANG Dong2, YU Jianmin2, LI Min2, LIU Tianqi2   

  1. 1. Weifang Medical College, Weifang 261053, Shandong, China;
    2. Department of Cardiac Surgery, Qianfoshan Hospital Affiliated to Shandong University, Shandong Heart Transplantation and Materials Engineering Technology Research Center, Jinan 250014, Shandong, China
  • Received:2015-01-12 Revised:2015-03-20 Online:2015-05-10 Published:2015-05-10

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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。

关键词: 心肌纤维化, 扩张型心肌病, microRNA-133, BCL-2

Abstract: Objective To investigate the effects of microRNA-133(miR-133) on myocardial fibrosis of dilated cardiomyopathy (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 fibroblasts 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 cardiac fibroblasts, 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.

Key words: microRNA-133, Dilated cardiomyopathy, BCL-2, Myocardial fibrosis

中图分类号: 

  • R542.2
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