Background: Studies have found that microRNAs (miRNAs) participate in the pathogenesis of myocardial ischemia-reperfusion injury (MIRI). miR-330-5p alleviated cerebral IR injury and regulated myocardial damage. However, the mechanism of the effect of miR-330-5p on MIRI needs to be further studied. Objective: The study aimed to explore the role and mechanism of miR-330-5p in MIRI. Methods: The oxygen-glucose deprivation reperfusion (OGD/R) model was constructed in cardiomyocytes to simulate MIRI in vitro. QRT-PCR was used for the detection of gene expression. ELISA was used for evaluation of the levels of aldehyde dehydrogenase 2 family member (ALDH2), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA). Flow cytometry was used to evaluate apoptosis. Western blot was employed for protein determination. Bioinformatic analysis was performed for predicting the targets of miR-330-5p. Results: miR-330-5p was found to be down-regulated in MIRI-induced cardiomyocytes (Model group). miR-330-5p mimic enhanced ALDH2 activity, inhibited apoptosis, and suppressed 4-HNE and MDA of MIRI-induced cardiomyocytes. miR-330-5p inhibited ERK expression while increasing the p38 expression. Bioinformatic analysis showed hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) to be a target of miR-330-5p. HSD11B1 expression was inhibited by miR-330-5p mimic while increased by miR-330-5p inhibitor in MIRI-induced cardiomyocytes. HSD11B1 overexpression reversed the effect of miR-330-5p on ALDH2, 4-HNE, MDA, apoptosis, and ERK/p38 signaling pathway. Furthermore, lncRNA small nucleolar RNA host gene 3 (SNHG3) was the upstream lncRNA of miR-330-5p. SNHG3 decreased miR-330-5p expression and increased HSD11B1 expression. Conclusion: SNHG3/miR-330-5p alleviated MIRI in vitro by targeting HSD11B1 to regulate the ERK/p38 signaling pathway.

中文翻译：

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SNHG3/miR-330-5p/HSD11B1 通过调节 ERK/p38 信号通路减轻心肌缺血再灌注损伤

背景：研究发现微小RNA（miRNA）参与心肌缺血再灌注损伤（MIRI）的发病机制。miR-330-5p减轻脑IR损伤并调节心肌损伤。但miR-330-5p对MIRI的影响机制还有待进一步研究。目的：探讨miR-330-5p在MIRI中的作用及机制。方法：构建心肌细胞氧糖剥夺再灌注（OGD/R）模型，模拟体外MIRI。QRT-PCR用于检测基因表达。使用 ELISA 评估乙醛脱氢酶 2 家族成员 (ALDH2)、4-羟基壬烯醛 (4-HNE) 和丙二醛 (MDA) 的水平。使用流式细胞术评估细胞凋亡。采用蛋白质印迹法测定蛋白质。进行生物信息学分析来预测 miR-330-5p 的靶标。结果：发现 MIRI 诱导的心肌细胞（模型组）中 miR-330-5p 下调。miR-330-5p 模拟增强 ALDH2 活性，抑制细胞凋亡，并抑制 MIRI 诱导的心肌细胞的 4-HNE 和 MDA。miR-330-5p 抑制 ERK 表达，同时增加 p38 表达。生物信息分析显示羟基类固醇 11-β 脱氢酶 1 (HSD11B1) 是 miR-330-5p 的靶标。在 MIRI 诱导的心肌细胞中，HSD11B1 表达被 miR-330-5p 模拟物抑制，而 miR-330-5p 抑制剂则增加。HSD11B1 过表达逆转了 miR-330-5p 对 ALDH2、4-HNE、MDA、细胞凋亡和 ERK/p38 信号通路的影响。此外，lncRNA小核仁RNA宿主基因3（SNHG3）是miR-330-5p的上游lncRNA。SNHG3 降低 miR-330-5p 表达并增加 HSD11B1 表达。结论：SNHG3/miR-330-5p通过靶向HSD11B1调节ERK/p38信号通路减轻MIRI。