Department of Cardiovascular Surgery, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Int J Mol Med. 2018 Jun;41(6):3221-3230. doi: 10.3892/ijmm.2018.3548. Epub 2018 Mar 7.
The aim of the present study was to determine the cardioprotective mechanisms by which micro (mi)RNA-30e protects the heart from myocardial ischemia/reperfusion injury (MI/R) and to explore the signaling pathways that may confer protection for the heart and be potential therapeutic targets. It was demonstrated that miRNA‑30e expression was decreased in patients with MI/R. In H9C2 cells, silencing (si)miRNA‑30e significantly inhibited cellular apoptosis, the expression of apoptosis regulator BAX (Bax) and caspase‑3 activity. It also significantly increased the expression of microtubule‑associated proteins 1A/1B light chain 3B, p62, Beclin‑1, neurogenic locus notch homolog protein‑1 (Notch1), Hes1 and phosphorylated‑protein kinase B (p‑Akt), and decreased the expression of inducible NO synthase (iNOS) and proteins associated with oxidative stress. The inhibition of autophagy following treatment with 3‑methyladenine significantly reversed the effect of si‑miRNA‑30e on apoptosis, Bax, caspase‑3, iNOS and oxidative stress in H9C2 cells. The promotion of Notch1 expression increased the effect of si‑miRNA‑30e on apoptosis, Bax, caspase‑3, iNOS, Notch1, Hes1 and p‑Akt protein expression and oxidative stress in H9C2 cells. Taken together, these results indicate that miRNA‑30e protects the heart from MI/R via autophagy and the Notch1/Hes1/Akt signaling pathway.
本研究旨在确定 micro (mi)RNA-30e 保护心脏免受心肌缺血/再灌注损伤 (MI/R) 的心脏保护机制,并探讨可能为心脏提供保护作用并成为潜在治疗靶点的信号通路。研究表明,miRNA-30e 在 MI/R 患者中的表达降低。在 H9C2 细胞中,沉默 (si)miRNA-30e 显著抑制细胞凋亡、凋亡调节因子 BAX (Bax) 和半胱天冬酶-3 活性的表达。它还显著增加微管相关蛋白 1A/1B 轻链 3B、p62、Beclin-1、神经源性基因座 Notch 同源蛋白-1 (Notch1)、Hes1 和磷酸化蛋白激酶 B (p-Akt) 的表达,并降低诱导型一氧化氮合酶 (iNOS) 和与氧化应激相关的蛋白的表达。用 3-甲基腺嘌呤处理后抑制自噬,可显著逆转 si-miRNA-30e 对 H9C2 细胞凋亡、Bax、半胱天冬酶-3、iNOS 和氧化应激的作用。促进 Notch1 表达增加了 si-miRNA-30e 对 H9C2 细胞凋亡、Bax、半胱天冬酶-3、iNOS、Notch1、Hes1 和 p-Akt 蛋白表达及氧化应激的作用。综上所述,这些结果表明 miRNA-30e 通过自噬和 Notch1/Hes1/Akt 信号通路保护心脏免受 MI/R。