miR-451对心肌细胞缺氧再复氧损伤的保护作用及其机制

发布时间：2018-07-25 14:51

【摘要】：目的探讨miR-451对心肌细胞缺氧再复氧损伤的保护作用及其心肌细胞高迁移率族蛋白1(HMGB1)表达变化。方法培养乳鼠心室肌细胞,制备缺氧再复氧模型,并随机分为对照组(Con组)、缺氧再复氧组(AR组)、AR+Ad-GFP组(空病毒组)、AR+Ad-miR-451组(miR-451上调组)、AR+Ad-asmiR-451组(miR-451下调组)。检测五组心肌细胞存活率、凋亡率以及HMGB1 mRNA、HMGB1和激活细胞凋亡蛋白酶3(caspase-3)表达水平。利用荧光素酶检测法在HEK293细胞中进一步确认miR-451对HMGB1作用靶点。结果与Con组比较,AR组、空病毒组、miR-451上调组、miR-451下调组心肌细胞存活率降低、凋亡率增高,心肌细胞HMGB1 mRNA、HMGB1、激活caspase-3表达增高(P均0.05)。与AR组比较,Ad-miR-451组心肌细胞存活率增高、凋亡率降低,心肌细胞HMGB1 mRNA、HMGB1、激活caspase-3表达降低(P均0.05)。miR-451识别HMGB1 mRNA的3'端非编码区并以此为作用靶点抑制HMGB1表达。结论上调miR-451对心肌细胞缺氧再复氧损伤有保护作用,此作用是通过miR-451抑制HMGB1 mRNA表达而实现的。
[Abstract]:Objective to investigate the protective effect of miR-451 on myocardial anoxia and reoxygenation injury and the change of high mobility group protein 1 (HMGB1) expression in cardiac myocytes. Methods the rat ventricular myocytes were cultured and the model of anoxic reoxygenation was prepared and divided into control group (group Con), anoxic reoxygenation group (group AR), AR+Ad-GFP group (air virus group), AR+Ad-miR-451 group (miR-). 451 up regulation group), group AR+Ad-asmiR-451 (miR-451 down-regulation). The survival rate, the rate of apoptosis and the expression of HMGB1 mRNA, HMGB1 and activated protease 3 (caspase-3) were detected in the five groups. The target of miR-451 to HMGB1 was further confirmed by luciferase detection in HEK293 cells. The results were compared with the Con group, AR group, and the empty virus group. In the up regulation group of miR-451, the survival rate of myocardial cells decreased, the rate of apoptosis increased, the myocardial cells HMGB1 mRNA, HMGB1, and the activation of Caspase-3 expression increased (P 0.05). Compared with the AR group, the survival rate of cardiac myocytes in the Ad-miR-451 group increased, the apoptosis rate decreased, the cardiomyocyte HMGB1 mRNA, HMGB1, the activation of the expression decreased (0.05). The non coding region of the 3'terminal of GB1 mRNA is used as a target to inhibit the expression of HMGB1. Conclusion up regulation of miR-451 has a protective effect on myocardial anoxia and reoxygenation damage. This effect is achieved through the inhibition of the expression of HMGB1 mRNA by miR-451.
【作者单位】：武汉大学人民医院;
【基金】：国家自然科学基金资助项目(81370308)
【分类号】：R542.2

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