Stomatin-like protein-2 (SLP-2) has emerged as a cytoprotective protein that confers a protective effect against various stresses. However, whether SLP-2 confers neuroprotection during cerebral ischemia/reperfusion injury remains unclear. In the present study, we investigated the role of SLP-2 in regulating oxygen-glucose deprivation/reoxygenation (OGD/R)-induced apoptosis and oxidative stress, which has been used as an in vitro model of cerebral ischemia/reperfusion injury. We found that OGD/R treatment resulted in a significant reduction in SLP-2 expression in neurons. Functional experiments demonstrated that SLP-2 overexpression significantly increased cell viability and decreased cell apoptosis and reactive oxygen species (ROS) production in OGD/R-exposed neurons, while SLP-2 inhibition showed the opposite effect. Notably, SLP-2 overexpression was shown to up-regulate the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). In addition, SLP-2 overexpression increased the nuclear expression of nuclear factor (erythroid-derived 2)-like 2 and reinforced the activity of Nrf2/antioxidant response element (ARE)-mediated transcription. However, AMPK inhibition or Nrf2/ARE inhibition partially reversed SLP-2-mediated neuroprotection effect in OGD/R-exposed neurons. Taken together, these results demonstrate that SLP-2 confers neuroprotection effect in OGD/R-injured neurons associated with reinforcing AMPK/Nrf2 signalling, suggesting SLP-2 as a potential therapeutic target for cerebral ischemia/reperfusion injury.

Stomatin-like protein-2 (SLP-2) 已成为一种细胞保护蛋白，可提供针对各种压力的保护作用。然而，SLP-2 是否在脑缺血/再灌注损伤期间赋予神经保护作用仍不清楚。在本研究中，我们研究了 SLP-2 在调节氧-葡萄糖剥夺/复氧 (OGD/R) 诱导的细胞凋亡和氧化应激中的作用，该作用已被用作体外脑缺血/再灌注损伤模型。我们发现 OGD/R 治疗导致神经元中 SLP-2 表达的显着降低。功能实验表明，SLP-2 过表达显着增加了 OGD/R 暴露神经元的细胞活力，减少了细胞凋亡和活性氧 (ROS) 的产生，而 SLP-2 抑制则显示出相反的效果。值得注意的是，SLP-2 过表达显示出上调单磷酸腺苷活化蛋白激酶 (AMPK) 的磷酸化。此外，SLP-2 过表达增加了核因子（红细胞衍生的 2）样 2 的核表达，并增强了 Nrf2/抗氧化反应元件 (ARE) 介导的转录的活性。然而，AMPK 抑制或 Nrf2/ARE 抑制部分逆转了 OGD/R 暴露神经元中 SLP-2 介导的神经保护作用。综上所述，这些结果表明 SLP-2 对 OGD/R 损伤神经元具有神经保护作用，与增强 AMPK/Nrf2 信号传导相关，表明 SLP-2 是脑缺血/再灌注损伤的潜在治疗靶点。