过表达microRNA-486对大鼠心肌梗死后心脏功能损伤的改善

摘要

Objective To investigate the effects of microRNA-486 (miR-486) expression on the cardiac function in rats with myocardial infarction (MI),through direct injection of an adenovirus carrying the miR-486 gene into the myocardium.Methods Totally 120 male rots were divided into 4 groups.Different target materials were infused into the surrounding areas of MI after building a successful disease model.Expression of miR-486 in the surrounding areas of left ventricular MI was detected using real-time PCR at different time points.Cardiac function was measured by cardiac ultrasound at 4 weeks.Using TUNEL,TTC,Masson,and CD31 staining to measure the organic changes in heart tissues.Results The expression of miR-486 in miR-486 group was higher than the other three groups.The expression of miR-486 in the three groups decreased when the time of MI in rats was prolonged.The cardiac function of the miR-486 group was better than that of the MI and AD groups.The MI area in the miR-486 group was smaller than that in the other two groups.Compared to the Sham group,the CVF at the infarct border zone was increased in the MI,Ad,and miR-486 groups.The AI in the MI and Ad groups was significantly increased compared to that in the miR-486 group.MVD was increased in the miR-486 group compared to that in the Sham,MI,and Ad groups.Conclusion miR-486 improved the cardiac function after MI in rats,through lightening collagen deposition,inhibiting apoptosis,and inducing angiogenesis in ischemic regions.%目的 观察直接心肌注射腺病毒搭载microRNA-486 (miR-486)基因对大鼠心肌梗死后心脏功能损伤的影响.方法 SD雄性大鼠,随机分成假手术组(Sham组)、心肌梗死+生理盐水组(MI组)、心肌梗死+空载腺病毒组(Ad组)、心肌梗死+miR-486腺病毒组(miR-486组).于梗死区周围心肌注射不同目标物质.于不同时间点利用实时定量聚合酶链式反应测量各组梗死周边区域miR-486表达水平.4周时行超声心动图检查,并取各组大鼠心脏行TTC染色,苏木精-依红(HE)染色,马松(Masson)染色,Tunel染色和免疫组化染色.结果 随着心肌梗死时间延长miR-486在3组内的含量有下降的趋势,但miR-486组miR-486表达量均较MI组和Ad组明显增加;超声心动图示miR-486组心功能优于MI组和Ad组;miR-486组心肌梗死面积较MI组、Ad组明显减少;Masson染色提示miR-486组、MI组和Ad组胶原容积分数(CVF)明显高于Sham组,但miR-486组CVF低于MI组和Ad组;MI组和Ad组心肌细胞凋亡指数显著上升但2组间比较差异无统计学意义,miR-486组与MI组和Ad组相比心肌细胞凋亡指数下降,Sham组未见明显心肌细胞凋亡;miR-486组微血管密度(MVD)显著高于Sham组、MI组和Ad组,且MI组、Ad组心肌MVD显著高于Sham组.结论 miR-486的心肌注射可通过抑制大鼠心肌梗死后纤维化,减少心肌细胞凋亡和促进缺血区域微血管新生,进而对心肌梗死后心脏功能有所改善.