BACKGROUND Previous in vitro studies demonstrated that suppression of microRNAs might protect cardiomyocytes and neurons against oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell apoptosis. However, whether the protective effect of miR-153-inhibition on cardiomyocytes can be observed in the animal model is unknown. We aimed to address this question using a rat model of ischemia-reperfusion (I/R). METHODS Rats were received the intramyocardial injection of saline or adenovirus-carrying target or control gene, and the rats were subjected to ischemia/reperfusion (I/R) treatment. The effects of miR-153 on I/R-induced inflammatory response and oxidative stress in the rat model were assessed using various assays. RESULTS We found that suppression of miR-153 decreased cleaved caspase-3 and Bcl-2-associated X (Bax) expression, and increased B cell lymphoma 2 (Bcl-2) expression. We further confirmed that Nuclear transcription factor erythroid 2-like 2 (Nrf2) is a functional target of miR-153, and Nrf2/Heme oxygenase-1 (HO-1) signaling was involved in miR-153-regulated I/R-induced cardiomyocytes apoptosis. Inhibition of miR-153 reduced I/R-induced inflammatory response and oxidative stress in rat myocardium. CONCLUSION Suppression of miR-153 exerts a cardioprotective effect against I/R-induced injury through the regulation of Nrf2/HO-1 signaling, suggesting that targeting miR-153, Nrf2, or both may serve as promising therapeutic targets for the alleviation of I/R-induced injury.

中文翻译：

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通过调节大鼠的Nrf2 / HO-1信号传导，抑制miR-153可以改善缺血/再灌注诱导的心肌细胞凋亡。

背景技术以前的体外研究表明，抑制microRNA可以保护心肌细胞和神经元免受氧葡萄糖剥夺和复氧（OGD / R）诱导的细胞凋亡。但是，在动物模型中是否可以观察到miR-153抑制作用对心肌细胞的保护作用尚不清楚。我们旨在使用大鼠缺血再灌注模型（I / R）解决此问题。方法大鼠心肌内注射生理盐水或携带腺病毒的靶标或对照基因，并进行缺血/再灌注（I / R）处理。使用多种试验评估了miR-153对I / R诱导的炎症反应和氧化应激的影响。结果我们发现抑制miR-153降低了裂解的caspase-3和Bcl-2相关X（Bax）表达，并增加B细胞淋巴瘤2（Bcl-2）的表达。我们进一步证实了核转录因子类红细胞2样2（Nrf2）是miR-153的功能靶标，并且Nrf2 / Heme氧化酶-1（HO-1）信号参与了miR-153调控的I / R诱导心肌细胞凋亡。抑制miR-153可降低I / R诱导的大鼠心肌炎症反应和氧化应激。结论miR-153的抑制通过调节Nrf2 / HO-1信号传导对I / R诱导的损伤具有心脏保护作用，表明靶向miR-153和/或Nrf2可能是缓解I的有希望的治疗靶点。 / R引起的损伤。Nrf2 /血红素加氧酶-1（HO-1）信号传导参与miR-153调控的I / R诱导的心肌细胞凋亡。抑制miR-153可降低I / R诱导的大鼠心肌炎症反应和氧化应激。结论miR-153的抑制通过调节Nrf2 / HO-1信号传导对I / R诱导的损伤具有心脏保护作用，表明靶向miR-153和/或Nrf2可能是缓解I的有希望的治疗靶点。 / R引起的损伤。Nrf2 /血红素加氧酶-1（HO-1）信号传导参与miR-153调控的I / R诱导的心肌细胞凋亡。抑制miR-153可降低I / R诱导的大鼠心肌炎症反应和氧化应激。结论miR-153的抑制通过调节Nrf2 / HO-1信号传导对I / R诱导的损伤具有心脏保护作用，表明靶向miR-153和/或Nrf2可能是缓解I的有希望的治疗靶点。 / R引起的损伤。