Department of Cardiovascular medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, Guizhou, 563002, P.R. China.
Protein Pept Lett. 2023;30(8):699-708. doi: 10.2174/0929866530666230721143705.
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.
The study aimed to explore the role and mechanism of miR-330-5p in MIRI.
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.
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.
SNHG3/miR-330-5p alleviated MIRI in vitro by targeting HSD11B1 to regulate the ERK/p38 signaling pathway.
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。然而，miR-330-5p 对 MIRI 的作用机制仍需进一步研究。
本研究旨在探讨 miR-330-5p 在 MIRI 中的作用及机制。
体外构建心肌细胞氧葡萄糖剥夺再灌注（OGD/R）模型模拟 MIRI。采用 QRT-PCR 检测基因表达。ELISA 法检测醛脱氢酶 2 家族成员（ALDH2）、4-羟基壬烯醛（4-HNE）和丙二醛（MDA）水平。流式细胞术检测细胞凋亡。Western blot 法检测蛋白表达。生物信息学分析预测 miR-330-5p 的靶基因。
MIRI 诱导的心肌细胞（模型组）中 miR-330-5p 表达下调。miR-330-5p 模拟物增强 ALDH2 活性，抑制细胞凋亡，抑制 MIRI 诱导的心肌细胞 4-HNE 和 MDA。miR-330-5p 抑制 ERK 表达，增加 p38 表达。生物信息学分析显示羟类固醇 11-β 脱氢酶 1（HSD11B1）是 miR-330-5p 的靶基因。miR-330-5p 模拟物抑制 MIRI 诱导的心肌细胞中 HSD11B1 的表达，而 miR-330-5p 抑制剂则增加其表达。HSD11B1 过表达逆转了 miR-330-5p 对 ALDH2、4-HNE、MDA、细胞凋亡及 ERK/p38 信号通路的影响。此外，长链非编码 RNA 小核仁 RNA 宿主基因 3（SNHG3）是 miR-330-5p 的上游 lncRNA。SNHG3 降低 miR-330-5p 的表达，增加 HSD11B1 的表达。
SNHG3/miR-330-5p 通过靶向 HSD11B1 调节 ERK/p38 信号通路缓解体外 MIRI。
