心肌梗死小鼠microRNAs表达及干预后心功能变化的研究

The expression of microRNAs in mice with myocardial infarction and the evaluation of cardiac function after intervention

目的检测小鼠心肌梗死后不同时间微小RNA(miRNA)-1及miRNA-21的表达,探讨miRNAs的表达和心肌重构及心功能变化的关系。方法取6周龄雄性小鼠采用结扎冠状动脉前降支中段制备小鼠心肌梗死模型,72只模型鼠分为模型组(MI组),干预1组(梗死区注射miRNA-1阻断剂)和干预2组(梗死区注射miRNA-21慢病毒载体),每组24只。分别于建模后4、8、12及16周每组各取6只动物采用超声仪检测心功能变化,评估心室重构程度。应用荧光定量PCR检测心肌组织中miRNA-1及miRNA-21基因表达变化。结果 (1)模型组miRNA-1的表达量在梗死4周时即升高,12周时表达最高,干预1组注射miRNA-1阻断剂后各时段miRNA-1表达降低。模型组miRNA-21在心肌梗死后4周表达略升高,后呈降低趋势,干预2组注射miRNA-21后,各时段miRNA-21均高表达。(2)沉默miRNA-1表达后干预1组小鼠心肌梗死8周及12周左室舒张末期内径(LVDD)缩小,左室射血分数(LVEF)于8周、12周及16周时有明显升高。miRNA-21过表达后干预2组心肌梗死12周时出现LVDD缩小,同时左室心肌质量(LVMass)及LVEF均有显著改善。结论 miRNA-1和miRNA-21可能在早期心力衰竭心室重构及心肌纤维化调控的过程中起重要的作用。

Objective To detect the expressions of miRNA-1 and miRNA-21 and to investigate the relationship between myocardial remodeling and changes of myocardial function.Methods The myocardial infarction model of mice were prepared.Seventy-two model mice were divided into model group(MI group),intervention group 1(miRNA-1 blocker was injected into infarct area)and intervention group 2(miRNA-21 lentivirus carrier was injected into infarct area),24 mice for each group.The ultrasonic instrument was used to measure the cardiac function indexes of the myocardial infarction model and evaluate the degree of cardiac function and ventricular remodeling.Fluorescence quantitative PCR was used to detect the expressions of miRNA-1 and miRNA-21.Results The expression of miRNA-1 was elevated at 4 weeks after MI,and reached the highest expression level at 12 weeks.The expression of miRNA-1 was decreased in all periods after the injection of miRNA-1 antagonist.MiRNA-21 showed a slight increase in 4 weeks after MI,followed by a decreasing trend.After injection of miRNA–21 lentiviral vectors,the elevated miRNA-21 expression was obtained at various times.After injection with miRNA-1 antagonist,LVDD and LVmass showed improvement in 8 weeks and 12 weeks after MI.LVEF was significantly improved in 8 weeks and 12 weeks.MiRNA-21 lentiviral vectors were injected,and LVDD was reduced in 12 weeks.LVmass and LVEF were significantly improved in 12 weeks after MI.Conclusion In the process of myocardial infarction,miRNA-1 and miRNA-21 are involved in the regulation of heart failure and ventricular remodeling.