Statins could reduce the risks of coronary heart disease death and ischemic cardiovascular events. In this study, we aim to explore the role of rosuvastatin in ischemia/reperfusion (I/R)-injured cardiomyocytes and the possible mechanism. An I/R model was established by oxygen-glucose deprivation/reperfusion (OGD/R). The protective effects of rosuvastatin pretreatment on OGD/R-injured cardiomyocytes were performed using MTT assay, lactate dehydrogenase (LDH) release assay, and quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics software TargetScan and miRTarBase were used to predict the targeted miRNAs with uncoupling protein (UCP)2. Furthermore, verify the binding capacity of hsa-miR-24-3p and UCP2 with qRT-PCR and dual-luciferase reporter assay. The expression of UCP2, cell viability, LDH level, and apoptosis level affected by downregulated hsa-miR-24-3p were assessed using qRT-PCR, western blotting, MTT, the LDH kit, and flow cytometry. Pretreatment with rosuvastatin could significantly augment cell viability, reduce LDH level, increase the expression of UCP2, and downregulate hsa-miR-24-3p in OGD/R-injured H9c2 cells. miR-24-3p was closely connected with UCP2, and downregulated miR-24-3p could promote UCP2 expression, which presented cell viability increasing, LDH release and cell apoptosis inhibition in OGD/R condition. Moreover, it decreased the protein expression of Cleaved-Caspase-9 and Cyto C. This is the first time our study suggests that rosuvastatin pretreatment protects cardiomyocytes from OGD/R through upregulating UCP2 through downregulation of hsa-miR-24-3p.

中文翻译：

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罗苏伐他汀通过下调Hsa-miR-24-3p靶向上调解偶联蛋白2减轻心肌细胞的缺血/再灌注损伤。

他汀类药物可以降低冠心病死亡和缺血性心血管事件的风险。在这项研究中，我们旨在探讨瑞舒伐他汀在缺血/再灌注（I / R）损伤的心肌细胞中的作用及其可能的机制。通过氧-葡萄糖剥夺/再灌注（OGD / R）建立了I / R模型。瑞舒伐他汀预处理对OGD / R损伤的心肌细胞的保护作用采用MTT分析，乳酸脱氢酶（LDH）释放分析和定量实时聚合酶链反应（qRT-PCR）进行。使用生物信息学软件TargetScan和miRTarBase来预测具有解偶联蛋白（UCP）2的靶向miRNA。此外，用qRT-PCR和双荧光素酶报告基因检测法验证hsa-miR-24-3p和UCP2的结合能力。UCP2的表达，细胞活力，LDH水平，使用qRT-PCR，western印迹，MTT，LDH试剂盒和流式细胞仪评估受hsa-miR-24-3p调节的细胞凋亡和凋亡水平。罗苏伐他汀预处理可以显着增强细胞活力，降低LDH水平，增加UCP2表达，并下调OGD / R损伤H9c2细胞中的hsa-miR-24-3p。miR-24-3p与UCP2密切相关，而下调的miR-24-3p可以促进UCP2表达，在OGD / R条件下，细胞活力增加，LDH释放和细胞凋亡抑制。此外，它降低了Cleaved-Caspase-9和Cyto C的蛋白质表达。这是我们的研究首次表明，瑞舒伐他汀预处理通过下调hsa-miR-24-3p上调UCP2，从而保护心肌细胞免受OGD / R侵害。免疫印迹，MTT，LDH试剂盒和流式细胞仪。罗苏伐他汀预处理可以显着增强细胞活力，降低LDH水平，增加UCP2表达，并下调OGD / R损伤H9c2细胞中的hsa-miR-24-3p。miR-24-3p与UCP2密切相关，而下调的miR-24-3p可以促进UCP2表达，在OGD / R条件下，细胞活力增加，LDH释放和细胞凋亡抑制。此外，它降低了Cleaved-Caspase-9和Cyto C的蛋白质表达。这是我们的研究首次表明，瑞舒伐他汀预处理通过下调hsa-miR-24-3p上调UCP2，从而保护心肌细胞免受OGD / R侵害。免疫印迹，MTT，LDH试剂盒和流式细胞仪。罗苏伐他汀预处理可以显着提高细胞活力，降低LDH水平，增加UCP2表达，并下调OGD / R损伤H9c2细胞中的hsa-miR-24-3p。miR-24-3p与UCP2密切相关，而下调的miR-24-3p可以促进UCP2表达，在OGD / R条件下，细胞活力增加，LDH释放和细胞凋亡抑制。此外，它降低了Cleaved-Caspase-9和Cyto C的蛋白质表达。这是我们的研究首次表明，瑞舒伐他汀预处理通过下调hsa-miR-24-3p上调UCP2，从而保护心肌细胞免受OGD / R侵害。增加OCP / R损伤的H9c2细胞中UCP2的表达，并下调hsa-miR-24-3p。miR-24-3p与UCP2密切相关，而下调的miR-24-3p可以促进UCP2表达，在OGD / R条件下，细胞活力增加，LDH释放和细胞凋亡抑制。此外，它降低了Cleaved-Caspase-9和Cyto C的蛋白表达。这是我们的研究首次表明，瑞舒伐他汀预处理通过下调hsa-miR-24-3p上调UCP2，从而保护心肌细胞免受OGD / R侵害。增加OCP / R损伤的H9c2细胞中UCP2的表达，并下调hsa-miR-24-3p。miR-24-3p与UCP2密切相关，而下调的miR-24-3p可以促进UCP2表达，在OGD / R条件下，细胞活力增加，LDH释放和细胞凋亡抑制。此外，它降低了Cleaved-Caspase-9和Cyto C的蛋白质表达。这是我们的研究首次表明，瑞舒伐他汀预处理通过下调hsa-miR-24-3p上调UCP2，从而保护心肌细胞免受OGD / R侵害。