MicroRNA-155/FOXO3a 在心脏手术后心房颤动 患者心房组织中的表达及与心房纤维化的关系

Expression of miR-155/FOXO3a axis in atrial tissue of patients with atrial fibrillation after cardiac surgery and its relationship with atrial fibrosis

摘要:

目的 探讨microRNA-155/ 叉头框蛋白O 3a（miR-155s/FOXO3a）在心脏手术后心房颤动（以 下简称房颤）患者心房组织中的表达情况，及其与心房纤维化的关系。方法 选取2018 年2 月—2019 年4 月 青海省心脑血管病专科医院收治的风湿性心脏瓣膜病并行心脏手术治疗的患者92 例。根据患者病史、心电 图及24 h 动态心电图检查结果分为房颤组和窦性心律组。于心脏手术中采集患者右心房组织，采用qRTPCR 检测心房组织中miR-155、FOXO3a mRNA 相对表达量；采用免疫印迹法检测心房组织中FOXO3a 和 p-FOXO3a 蛋白相对表达量；采用Masson 染色法及计算机成像分析系统计算心房组织胶原容积分数，评价心 房组织纤维化程度；采用Pearson 法分析心房组织miR-155、p-FOXO3a 蛋白水平与心房纤维化程度的相关 性。结果 房颤组左心房内径、右心房内径高于窦性心律组（P <0.05）。房颤组胶原容积分数较窦性心律组 高（P <0.05）。窦性心律组miR-155 mRNA 相对表达量低于房颤组（P <0.05），FOXO3a mRNA 相对表达量 高于房颤组（P <0.05）。房颤组p-FOXO3a 蛋白相对表达量低于窦性心律组（P <0.05）。房颤组患者心房组 织miR-155 水平与p-FOXO3a 蛋白水平呈负相关（r =-0.485，P <0.05），与胶原容积分数呈正相关（r =0.490， P <0.05），心房组织p-FOXO3a 蛋白水平与胶原容积分数呈负相关（r =-0.471，P <0.05）。结论 心脏手术后房 颤患者心房组织中miR-155高表达，p-FOXO3a蛋白低表达，均与心房纤维化有关，共同影响房颤的发生与维持。

Abstract:

Objective To investigate the expression of microRNA-155/fork-head box protein O 3a (microRNA-155/FOXO 3a) axis in atrial tissue of patients with atrial fibrillation after cardiac surgery and its relationship with atrial fibrosis. Methods Ninety two patients with rheumatic valvular heart disease who underwent cardiac surgery in Qinghai Provincial Cardiovascular and Cerebrovascular Disease Hospital from February 2018 to April 2019 were selected and divided into atrial fibrillation group (43 cases) and sinus rhythm group (49 cases) according to their medical history, electrocardiogram (ECG) and 24-hour dynamic electrocardiogram (DCG). Right atrial tissue was collected during cardiac surgery, real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of microRNA-155 and FOXO3a in atrial tissue, the expression levels of FOXO3a and p-FOXO3a in atrial tissue were detected by immunoblotting (WB), the collagen volume fraction (CVF) of atrial tissue was calculated by Masson staining and computer imaging analysis system to evaluate the degree of atrial fibrosis, and Pearson method was used to analyze the correlations of microRNA-155, p-FOXO3a protein levels and CVF in atrial tissue. Results Compared with sinus rhythm group, the diameters of left atrium and right atrium increased significantly, the level of microRNA-155 and CVF in atrial tissue increased significantly, and the levels of FOXO3a mRNA and p-FOXO3a protein decreased significantly (all P < 0.05). The levels of microRNA-155 and p-FOXO3a protein in atrial tissue were negatively correlated (r = -0.485, P < 0.05), while the levels of microRNA-155 in atrial tissue were positively correlated with CVF (r = 0.490, P < 0.05), and the level of p-FOXO3a protein in atrial tissue was negatively correlated with CVF (r = -0.471, P < 0.05). Conclusions The high expression of microRNA-155 and low expression of p-FOXO3a protein in atrial tissue of patients with atrial fibrillation after cardiac surgery are both related to atrial fibrosis, which affect the occurrence and maintenance of atrial fibrillation jointly.