Oxidative stress is believed to be one of the primary causes in ischemic stroke injury, and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is the most important endogenous antioxidative stress damage pathway. Cottonseed oil (CSO), which is used mostly as a solvent for lipid-soluble drugs, has been shown to exert antioxidative effects against peripheral tissue injury. However, the effects and mechanisms of CSO on ischemic stroke-induced oxidative stress injury and the Nrf2 signaling pathway remain largely unknown. In this study, we investigated the potential of CSO in regulating oxidative stress injury induced by middle cerebral artery occlusion and reperfusion (MCAO-R), or oxygen and glucose deprivation and reperfusion (OGD-R). We found that 1.3 mL/kg CSO treatment of male rats with a subcutaneous injection once every other day for 3 weeks significantly improved neurological deficit; reduced infarction volume; alleviated neuronal injuries; reduced the content of ROS and MDA; increased the activity of SOD, GSH, and GSH-PX; and markedly increased the expression of Nrf2. Furthermore, treatment with 10⁻⁹ μL/mL CSO to a neuron cell line (HT-22) for 24 h significantly increased cell viability and decreased cell apoptosis after OGD-R injury; significantly reduced the levels of ROS and MDA; increased the activity of SOD, GSH, and GSH-PX; and induced an increase in Nrf2 nuclear translocation. Based on our findings, we conclude that CSO treatment alleviates ischemic stroke injury-induced oxidative stress via activating the Nrf2 signaling pathway, highlighting the potential that CSO has as a therapeutic for ischemic strokes.

氧化应激被认为是缺血性脑卒中损伤的主要原因之一，而核因子红细胞2相关因子2（Nrf2）信号通路是最重要的内源性抗氧化应激损伤通路。棉籽油 (CSO) 主要用作脂溶性药物的溶剂，已被证明对周围组织损伤具有抗氧化作用。然而，CSO对缺血性中风引起的氧化应激损伤和Nrf2信号通路的影响和机制仍知之甚少。在这项研究中，我们研究了 CSO 在调节大脑中动脉闭塞和再灌注 (MCAO-R) 或缺氧和葡萄糖剥夺和再灌注 (OGD-R) 引起的氧化应激损伤中的潜力。我们发现，雄性大鼠皮下注射1.3 mL/kg CSO，每隔一天注射一次，持续3周，神经功能缺损得到显着改善；减少梗塞体积；减轻神经元损伤；降低ROS和MDA含量；增加SOD、GSH和GSH-PX的活性；并显着增加Nrf2的表达。此外，用10 ^-9 μL/mL CSO处理神经元细胞系（HT-22）24小时显着增加OGD-R损伤后的细胞活力并减少细胞凋亡。显着降低ROS和MDA水平；增加SOD、GSH和GSH-PX的活性；并诱导 Nrf2 核易位增加。根据我们的研究结果，我们得出结论，CSO 治疗通过激活 Nrf2 信号通路减轻缺血性中风损伤诱导的氧化应激，这凸显了 CSO 作为缺血性中风治疗的潜力。