风湿性二尖瓣疾病合并心房颤动患者心房纤维化相关微小RNA-647及预测靶基因研究  

Atrial fibrosis-related miR-647 and its predictive target genes in patients with rheumatic mitral valve disease and atrial fibrillation

作　　者：韩丹[1] 罗超迪 闫炀[1] HAN Dan;LUO Chaodi;YAN Yang(Department of Cardiovascular Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061;Department of Cardiology,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安交通大学第一附属医院心血管外科,710061 [2]西安交通大学第一附属医院心血管内科,710061

出　　处：《国际心血管病杂志》2022年第4期228-234,共7页International Journal of Cardiovascular Disease

基　　金：陕西省自然科学基础研究计划(2021JQ-394)。

摘　　要：目的:明确风湿性二尖瓣疾病合并心房颤动(房颤)患者心房组织的主要病理变化,生物信息学分析并筛选与风湿性二尖瓣疾病房颤患者心房纤维化相关的微小RNA(miRNA)及其靶基因。方法:收集在西安交通大学第一附属医院行心脏外科手术治疗的30例风湿性二尖瓣疾病患者(窦性心律组10例,房颤组20例)的临床资料及心房样本。苏木精-伊红染色、Masson染色、免疫组织化学染色后观察心房组织病理变化;实时定量聚合酶链反应及Western blot法检测纤维化相关蛋白和通路在心房组织中的表达;生物信息学分析并筛选出与风湿性二尖瓣疾病房颤发病机制相关的miR-647及其预测靶基因PRKCA;进一步应用双荧光素酶报告基因确定miR-647的靶基因为PRKCA。结果:相较于窦性心律组患者,房颤组患者左房组织具有典型的心房肌肥大、间质纤维化、心房肌细胞坏死等病理改变;房颤组患者左房纤维化蛋白及通路表达水平显著高于窦性心律组(P均<0.05);生物信息学筛选出风湿性二尖瓣疾病房颤相关miR-647及其纤维化相关的下游靶基因PRKCA;房颤组左房组织中miR-647明显下调,PRKCA表达则明显升高(P均<0.05);双荧光素酶报告基因实验验证miR-647对靶基因PRKCA具有明显的抑制作用(P<0.05)。结论:miR-647靶向作用于PRKCA基因,与风湿性二尖瓣疾病房颤患者的心房纤维化有关。Objective:To identify the main pathological changes of atrial tissue in patients with rheumatic mitral valve disease(RMVD)and atrial fibrillation(AF),and to analyze and screen miRNAs and their target genes associated with atrial fibrosis in patients with rheumatic mitral valve disease and atrial fibrillation.Methods:The clinical data and atrial samples of 30 patients with rheumatic mitral valve disease(10 in the sinus rhythm group and 20 in the atrial fibrillation group)who underwent cardiac surgery in the First Affiliated Hospital of Xi'an Jiaotong University were collected.Hematoxylin-eosin staining,Masson staining and immunohistochemical staining were used to observe the pathological changes of atrial tissue.Real-time quantitative polymerase chain reaction and western blot were used to detect the expression levels of fibrosis-related proteins and pathways in atrial tissue.MiR-647 and its predicted target gene PRKCA related to the pathogenesis of rheumatic mitral valve disease atrial fibrillation were screened out by bioinformatics analysis.The dual luciferase reporter gene was further used to determine the target gene of miR-647 as PRKCA.Results:Compared with the sinus rhythm group,the left atrial tissue of the AF group had typical pathological changes such as atrial muscle hypertrophy,interstitial fibrosis,atrial myocyte necrosis,and the expression levels of left atrial fibrosis proteins and pathways were significantly increased in the AF group(all P<0.05).Bioinformatics screened the rheumatic mitral valve disease atrial fibrillation-related miR-647 and its fibrosis-related downstream target gene PRKCA.MiR-647 was significantly down-regulated in the left atrial tissue of the AF group,while the expression of PRKCA was significantly increased(all P<0.05).The dual-luciferase reporter gene experiment verified that miR-647 had a significant inhibitory effect on the target gene PRKCA(P<0.05).Conclusion:MiR-647 targets the PRKCA and is associated with atrial fibrosis in patients with rheumatic mitral valve disease a

关 键 词：心房颤动 心房纤维化 生物信息学 微小RNA-647 PRKCA基因 

分 类 号：R541.75[医药卫生—心血管疾病] R542.51[医药卫生—内科学]