miR-451对心肌细胞缺氧再复氧损伤的保护作用及其机制  

Protective effect of miR-451 on anoxia/reoxygenation injury in cardiomyocytes

作　　者：胡笑容[1] 谢菁[1] 马瑞松 廖芫熙[1] 李雪飞[1] 江洪[1] HU Xiaorong XIE Jing MA Ruisong LIAO Yuanxi LI Xuefei JIANG Hong(Renmin Hospital of Wuhan University, Wuhan 430060, Chin)

机构地区：[1]武汉大学人民医院,武汉430060

出　　处：《山东医药》2017年第17期1-3,共3页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81370308)

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。Objective To investigate the protective effect of microRNA-451 （miR-451） on anoxia/reoxygenation （A/ R） injury in cardiomyotes and high mobility group box 1 protein （HMGB1） expression. Methods Neonatal rat ventricular eardiomyocytes were prepared and then subjected to A/R injury. Then they were divided into the control group （Con group ）, anoxia and reoxygenation group （ AR group）, AR ＋ Ad-GFP group （ empty virus group）, AR ＋ Ad-miR-451 group （miR-451 up-regulation group）, AR ＋ Ad-asmiR -451 group （miR-451 down-regulation group）. We detected the cell viability, apoptosis rate, and the expression of Caspase-3 and HMGB1, HMGB1 mRNA. The luciferase assay was performed to further confirm MiR-451 targets for HMGB1. Results Compared with the Con group l the cell Viability decreased, apoptosis index （AI） and the expression of Caspase-3, HMGB1 and HMGB1 mRNA increased in the other four groups （ all P 〈 0.05）. Compared with AR group, cell viability increased, apoptosis index （AI） and the expression of Caspase-3, HMGB1 and HMGB1 mRNA decreased in the Ad-miR-451 group （all P 〈0.05）. The luciferase assay confirmed that the 31JTR of HMGB1 mRNA was a direct target of miR-451 in cardiomyocytes, which inhibited the expression of HMGB1. Conclusion The up-regulation of miR-451 could protect A/R injury-induced cardiomyocytes by inhibiting HMGB1 expression through miR-451.

关 键 词：心肌细胞 缺氧再复氧损伤 微小RNA-451 高迁移率族蛋白1 

分 类 号：R541.4[医药卫生—心血管疾病]