Myocardial ischaemia reperfusion injury (MIRI) is a difficult problem in clinical practice, and it may involve various microRNAs. This study investigated the role that endogenous microRNA-146a plays in myocardial ischaemia reperfusion and explored the possible target genes. MIRI models were established in microRNA-146a deficient (KO) and wild type (WT) mice. MicroRNA-146a expression was evaluated in the myocardium of WT mice after reperfusion. The heart function, area of myocardium infarction and in situ apoptosis were compared between the KO and WT mice. Microarray was used to explore possible target genes of microRNA-146a, while qRT-PCR and dual luciferase reporter assays were used for verification. Western blotting was performed to detect the expression levels of the target gene and related signalling molecules. A rescue study was used for further testing. MicroRNA-146a was upregulated 1 h after reperfusion. MicroRNA-146a deficiency decreased heart function and increased myocardial infarction and apoptosis. Microarray detected 19 apoptosis genes upregulated in the KO mice compared with the WT mice. qRT-PCR and dual luciferase verified that Med1 was one target gene of microRNA-146a. TRAP220, encoded by Med1 in the KO mice, was upregulated, accompanied by an amplified ratio of Bax/Bcl2 and increased cleaved caspase-3. Inhibition of microRNA-146a in H9C2 cells caused increased TRAP220 expression and more apoptosis under the stimulus of hypoxia and re-oxygenation, while knockdown of the increased TRAP220 expression led to decreased cell apoptosis. MicroRNA-146a exerts a protective effect against MIRI, which might be partially mediated by the target gene Med1 and related to the apoptosis signalling pathway.

中文翻译：

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MicroRNA-146a 通过靶向 Med1 来防止心肌缺血再灌注损伤。

心肌缺血再灌注损伤（MIRI）是临床上的难题，可能涉及多种microRNA。本研究调查了内源性 microRNA-146a 在心肌缺血再灌注中的作用，并探讨了可能的靶基因。在 microRNA-146a 缺陷 (KO) 和野生型 (WT) 小鼠中建立 MIRI 模型。再灌注后在 WT 小鼠的心肌中评估 MicroRNA-146a 的表达。比较KO和WT小鼠的心功能、心肌梗死面积和原位凋亡情况。微阵列用于探索 microRNA-146a 的可能靶基因，而 qRT-PCR 和双荧光素酶报告基因检测用于验证。Western blotting检测目的基因及相关信号分子的表达水平。救援研究用于进一步测试。再灌注后 1 小时，MicroRNA-146a 上调。MicroRNA-146a 缺乏会降低心脏功能并增加心肌梗塞和细胞凋亡。与 WT 小鼠相比，微阵列检测到 KO 小鼠中上调的 19 个凋亡基因。qRT-PCR 和双荧光素酶证实 Med1 是 microRNA-146a 的靶基因之一。在 KO 小鼠中由 Med1 编码的 TRAP220 被上调，伴随着 Bax/Bcl2 的放大率和切割的 caspase-3 增加。在缺氧和再氧化的刺激下，H9C2 细胞中 microRNA-146a 的抑制导致 TRAP220 表达增加和更多的细胞凋亡，而 TRAP220 表达增加的敲低导致细胞凋亡减少。MicroRNA-146a 对 MIRI 具有保护作用，