心房颤动患者心房组织中微小RNA-21和金属基质蛋白酶-2表达水平改变及意义

目的检测微小RNA（microRNA）-21及其调控的金属基质蛋白酶-2（MMP-2）在心房颤动（房颤）患者心房组织中的表达变化，探讨房颤患者心房结构重构的分子机制。方法26例风湿性心脏瓣膜病接受瓣膜置换术患者分为两组，其中窦性心律组12例，慢性房颤组14例。于术中获取右心耳组织，采用荧光定量聚合酶链反应（PCR）检测心肌组织中microRNA-21的相对表达量，用免疫印迹法及免疫组织化学染色法检测MMP-2蛋白水平及分布。用Masson染色检测心肌胶原容积。结果房颤组心房肌组织microRNA-21及MMP-2表达水平明显增加microRNA-21：房颤组（2．23±0．31）与窦性心律组（0．94±0．24），P〈0．01；MMP-2：房颤组（0．93±0．04）与窦性心律组（0．87±0．05），P〈0．01]。microRNA-21表达水平与左心房内径呈正相关（r=0．429，P〈0．05）。房颤患者心房组织胶原纤维含量明显增加房颤组（14．1％±0．01％）与窦性心律组（8．3％±0．01％），P〈0．01]。MMP-2蛋白表达水平分别与左心房内径呈正相关（r=0．471，P〈0．05），与心肌胶原容积分数呈正相关（r=0．456；P〈0．05）。结论房颤患者心房组织中microRNA-21表达增高及正向上调MMP-2蛋白水平可能是影响胶原代谢、造成房颤时心房结构重构的分子机制之一，与房颤的发生和维持有关。

MicroRNA-21 and matrix metalloprotease-2 in patients with rheumatic valvular heart disease and atrial fibrillation

Objective To investigate changes of micmRNA-21 expressions in right auricle in patients with rheumatic heart disease and atrial fibrillation(AF).Methods Right atrial appendages were obtained from 12 rheumatic valvular heart disease patients with sinus rhythm(SR)and 14 patients with chronic AF.Quantitative real time polymerase chain reaction(qRT-PCR)was applied to assess expressions of microRNA-21.Proteins were quantified from immunoblots.Immunohistochemistry was applied to localize MMP-2 and Masson staining was used to estimate collagen deposition.Results Expressions of microRNA-21 was increased(relative expression:2.23±0.31 vs.0.94±0.24;P<0.01)in AF patients.There was a corresponding increased MMP-2 procollagen volume fraction CVF:14.1%±0.01%vs.8.3%±0.01%;P<0.01).Expression of MicroRNA-21 was positively correlated to left atrium dimension(r=0.429;P<0.05).Expression of MMP-2 was positively correlated to collagen content(r=0.456,P<0.05)and left atrium dimension(r=0.471;P<0.05).Conclusion Expression of microRNA-21 level was significantly up-regulated in human patients with AF,possibly contributing to up-regulation of MMP-2 leading to increased collagen content in the atrium.These results provide potential new insights into molecular mechanisms of AF.