Department of Anesthesiology, Heze Municipal Hospital, Heze, Shandong 274031, P.R. China.
Mol Med Rep. 2018 Sep;18(3):3497-3505. doi: 10.3892/mmr.2018.9315. Epub 2018 Jul 24.
Melatonin can protect against cardiac ischemia/reperfusion (I/R) injury in models in vitro and in vivo by regulating oxidative stress and apoptosis; however, the precise molecular mechanisms involved remain unclear. Nuclear factor erythroid 2‑related factor 2 (Nrf2) is a transcription factor, which has been associated with the regulation of oxidative stress by translocating to the nucleus. Therefore, the present study investigated whether activation of the Nrf2 signaling pathway may be responsible for the protective effects of melatonin on I/R‑injured cardiomyocytes. In the present study, H9c2 cells were subjected to simulated I/R (SIR) injury and pretreated with melatonin and/or Nrf2 small interfering RNA (siRNA). Cell viability was detected via Cell Counting kit‑8 assay, apoptosis was examined by caspase‑3 cleavage and activity analysis; oxidative stress levels were determined by specific activity analysis assays. In the present study, it was observed that SIR induced significant increases in apoptosis and oxidative stress, and enhanced Nrf2 expression within H9c2 cells. Pretreatment with melatonin partially reversed these alterations and promoted Nrf2 nuclear translocation. Transfection with Nrf2 siRNA inhibited the protective effects of melatonin on SIR‑induced H9c2 cells. These results indicated that melatonin may protect H9c2 cells against I/R injury by reducing apoptosis and oxidative stress; this effect may be mediated via activation of the Nrf2 signaling pathway. Collectively, the results of the present study may suggest melatonin as a potential therapeutic agent against cardiac I/R injury.
褪黑素通过调节氧化应激和细胞凋亡来保护体外和体内的心肌缺血/再灌注（I/R）损伤；然而，其涉及的确切分子机制仍不清楚。核因子红细胞 2 相关因子 2（Nrf2）是一种转录因子，通过向核内易位与氧化应激的调节有关。因此，本研究探讨了 Nrf2 信号通路的激活是否可能是褪黑素对 I/R 损伤心肌细胞保护作用的机制。在本研究中，将 H9c2 细胞进行模拟 I/R（SIR）损伤，并经褪黑素和/或 Nrf2 小干扰 RNA（siRNA）预处理。通过 Cell Counting kit-8 检测试剂盒检测细胞活力，通过 caspase-3 切割和活性分析检测细胞凋亡；通过特定活性分析测定氧化应激水平。在本研究中，观察到 SIR 诱导 H9c2 细胞内凋亡和氧化应激显著增加，并增强 Nrf2 表达。褪黑素预处理部分逆转了这些改变，并促进了 Nrf2 的核易位。Nrf2 siRNA 的转染抑制了褪黑素对 SIR 诱导的 H9c2 细胞的保护作用。这些结果表明，褪黑素可能通过减少细胞凋亡和氧化应激来保护 H9c2 细胞免受 I/R 损伤；这种作用可能是通过激活 Nrf2 信号通路介导的。综上所述，本研究的结果可能表明褪黑素是一种治疗心肌 I/R 损伤的潜在治疗剂。
