【摘要】 目的:研究microRNA-24(miR-24)在心肌梗死小鼠心肌组织中的表达变化,并研究miR-24对心肌细胞凋亡及心肌梗死后心功能的调控作用。方法:建立小鼠心梗模型及心肌细胞缺血缺氧模型,qRT-PCR检测心梗后心肌组织中miR-24表达情况;构建携带miR-24的慢病毒及脂质体,心梗组织局部注射慢病毒转染miR-24及心肌原代细胞转染miR-24;caspase-3/7检测心肌细胞凋亡情况;超声心动图及Masson染色检测心功能及心梗面积;TUNEL染色检测细胞凋亡;表达谱芯片检测及生物信息学分析预测靶位点。结果:miR-24在心梗部位及心梗周边区表达显著降低(P<0.01),心梗模型转染miR-24能够改善心梗后2周心功能(P<0.05),并减少心梗面积,抑制心梗局部细胞凋亡水平;原代心肌细胞转染miR-24能减少缺血缺氧引起的细胞凋亡(P<0.01),芯片检测发现miR-24可能通过BCL2L11、ANK3及SGPL1等基因起作用。结论:miR-24在心梗后心肌组织中低表达。miR-24能抑制心肌细胞缺血缺氧条件下的凋亡水平,进而改善心梗后心功能。更多还原

【Abstract】 AIM: To evaluate the expression of miR-24 in infarcted myocardial tissues and to investigate the function of miR-24 during cardiomyocyte apoptosis in vitro and in vivo.METHODS: The mouse model of myocardial infarcton(MI) was established.The expression of miR-24 in the sections of infarcted myocardial tissues was measured by qRT-PCR.The expression of miR-24 was modified by transfecting oligonucleotide mimic and inhibitor of miR-24 into cardiomyocytes,or injecting lentiviral vectors intramyocardially.The apoptosis of cardiomyocytes was detected by Caspase-Glo 3/7 Assay System.The heart functions were determined by echocardiography and the scar size in MI model was observed with Masson trichrome staining.The apoptosis of infarcted myocardial tissues was detected by TUNEL method.Microarray and bioinformatic analysis were also used to predict the targets of miR-24.RESULTS: The expression of miR-24 in the infarct and border areas was down-regulated after MI.Overexpression of miR-24 in cardiomyocytes reduced the apoptosis induced by hypoxia.miR-24 transfection resulted in reduction of the scar size,and improved left ventricular fractional shortening(LVFS) and left ventricular ejection fraction(LVEF) of the mice in treatment group after 2 weeks.Furthermore,miR-24 reduced cell apoptosis in the infarct region.BCL2L11,ANK3 and SGPL1 may be the targets of miR-24 during the process of anti-apoptosis.CONCLUSION: miR-24 is down-regulated in the infarcted myocardial tissues.In vitro,miR-24 reduces apoptosis of cardiomyocytes induced by hypoxia.In vivo,miR-24 attenuates cell apoptosis in the infarct and border areas of the heart 2 weeks after MI,and ultimately improves heart functions.更多还原