miR-139-5p与心力衰竭的相关性研究  

Correlation between miR-139-5p and heart failure

作　　者：杨子瑶 陈彦丽 苏明 赵晓涛[1] YANG Zi-yao;CHEN Yan-li;SU Ming;ZHAO Xiao-tao

机构地区：[1]北京大学人民医院检验科,北京市100044

出　　处：《中国分子心脏病学杂志》2022年第1期4475-4480,共6页Molecular Cardiology of China

基　　金：国家自然科学基金(81500236,81870196)。

摘　　要：目的探讨miR-139-5p在心肌重塑中的作用,分析循环miR-139-5p在心肌重塑及心力衰竭中的表达水平。方法收集33例心力衰竭患者和27例健康对照的血浆样本,依据左室射血分数(left ventricular ejection fraction,LVEF)对心力衰竭患者进行分层。构建两种自发性心肌重塑伴心力衰竭小鼠模型。通过实时荧光定量PCR检测小鼠血清和患者血浆中miR-139-5p的表达水平。采用阿霉素处理原代新生大鼠心肌细胞(neonatal rat cardiac myocytes,NRCM),同时转染miR-139-5p,采用CCK-8法检测NRCM活力,荧光显微镜下观察NRCM形态。结果心力衰竭患者血浆miR-139-5p的表达水平与健康对照组无显著差异。但在亚群分析中,LVEF≤40%组血浆miR-139-5p表达水平显著高于LVEF>40%组(Z=2.738,P=0.005),LVEF≤40%组血浆miR-139-5p表达水平与CK-MB正相关(ρ=0.526,P=0.03)。血浆miR-139-5p能够帮助心力衰竭患者分层。在两种自发性心肌重塑伴心力衰竭小鼠心肌组织中miR-139-5p显著下调(t=2.476,P=0.035;t=2.946,P=0.016),而阿霉素诱导的小鼠心力衰竭模型中血清miR-139-5p则无显著变化。过表达miR-139-5p可部分拮抗ADR诱导NRCM活力下降及形变。结论循环miR-139-5p与心力衰竭中左室收缩功能障碍有关,miR-139-5p能够抑制心肌损伤。Objective To investigate the role of miR-139-5p in myocardial remodeling and to analyze circulating miR-139-5p expression in myocardial remodeling and heart failure.Methods We recruited 33 heart failure patients and 27 healthy controls.According to the left ventricular ejection fraction(LVEF),33 patients with heart failure were divided into two groups.The plasma miR-139-5p was detected using real-time quantitative PCR detecting system.The spontaneous myocardial remodeling with heart failure mice model and adriamycin-induced cardiac remodeling mice model were established.Then the expression of miR-139-5p in heart or circulatory was determined using real-time qPCR.Neonatal rat cardiac myocytes(NRCM)were transfected with miR-139-5p and co-treated with ADR.The NRCM viability was tested using CCK-8 assay,and the morphology of NRCM was observed by fluorescence microscopy.Results The circulating miR-139-5p levels in heart failure patients’plasma and healthy controls were comparable.However,the expression level of miR-139-5p in LVEF≤40%group was significantly higher than that in HFmrEF group(Z=2.738,P=0.005).The expression level of plasma miR-139-5p was positively correlated with CK-MB in LVEF≤40%patients(ρ=0.526,P=0.03),and effective in diagnosing the presence of left ventricular dysfunction in heart failure.MiR-139-5p was significantly down-regulated in heart tissue of spontaneous myocardial remodeling of spontaneous myocardial remodeling with heart failure mice(t=2.476,P=0.035;t=2.946,P=0.016),while the change in serum expression of miR-139-5p of adriamycin-treated mice was not statistically significant.Overexpression of miR-139-5p in NRCM partially rescued ADR-induced cardiomyocyte activity decline and morphological changes.Conclusion Circulating miR-139-5p is correlated with left ventricular dysfunction in heart failure,miR-139-5p partially rescued cardiomyocyte injury.

关 键 词：心力衰竭 MICRORNA miR-139-5p 心肌损伤 

分 类 号：R541.6[医药卫生—心血管疾病]