microRNA-130a-5p 通过下调 HMGB2/NF-κB 轴抑制心肌缺血再灌注损伤。

BACKGROUND: Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. METHODS: MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. RESULTS: Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. CONCLUSION: Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.

背景：心肌缺血再灌注损伤（MIRI）定义为急性冠状动脉闭塞后缺血性心肌中进行性加重的病理过程中的组织损伤。研究已经证明 microRNAs（miRs）参与了 MIRI。然而，miR-130a-5p 在 MIRI 中的作用尚不清楚。本研究旨在探讨 miR-130a-5p 对 MIRI 的影响。

方法：建立 MIRI 小鼠模型。然后，使用超声心动图和多导生理记录仪检测心功能和血流动力学。采用 miR-130a-5p 功能测定法检测氧化应激、线粒体功能、炎症和细胞凋亡程度。苏木精和伊红（HE）染色验证小鼠心肌损伤。采用逆转录定量聚合酶链反应（RT-qPCR）评估 miR-130a-5p、高迁移率族蛋白 B2（HMGB）2 和核因子 kappa-B（NF-κB）的表达模式。然后，进行双荧光素酶报告基因检测以阐明 miR-130a-5p 与 HMGB2 之间的靶向关系。

结果：HE 染色显示 MIRI 小鼠模型结构排列紊乱。RT-qPCR 显示，过表达 miR-130a-5p 减轻了 MIRI、MIRI 诱导的氧化应激和小鼠线粒体紊乱。接下来，确定了 miR-130a-5p 与 HMGB2 之间的靶向关系。过表达 HMGB2 消除了 miR-130a-5p 在 MIRI 小鼠中的保护作用。此外，miR-130a-5p 通过下调核因子 kappa-B（NF-κB）轴靶向 HMGB2，减轻 MIRI 引起的炎症损伤。

结论：本研究表明，miR-130a-5p 通过下调 HMGB2/NF-κB 轴抑制 MIRI。这项研究可能为 MIRI 治疗的发展提供新的思路。