Liu Min, Li Hao, Zhang Lixia, Xu Zhipeng, Song Yuxiang, Wang Xiaoyan, Chu Ruitong, Xiao Yunming, Sun Miao, Ma Yulong, Mi Weidong
Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
Department of Burn and Plastic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China.
Mol Neurobiol. 2021 Jun;58(6):2494-2507. doi: 10.1007/s12035-020-02256-y. Epub 2021 Jan 14.
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 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对缺血性脑卒中诱导的氧化应激损伤和Nrf2信号通路的影响及机制仍 largely未知。在本研究中,我们研究了CSO在调节大脑中动脉闭塞再灌注(MCAO-R)或氧糖剥夺再灌注(OGD-R)诱导的氧化应激损伤中的潜力。我们发现,以1.3 mL/kg的剂量对雄性大鼠每隔一天皮下注射一次CSO,持续3周,可显著改善神经功能缺损;减少梗死体积;减轻神经元损伤;降低活性氧(ROS)和丙二醛(MDA)的含量;增加超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-PX)的活性;并显著增加Nrf2的表达。此外,用10 μL/mL的CSO处理神经元细胞系(HT-22)24小时,可显著提高OGD-R损伤后的细胞活力并减少细胞凋亡;显著降低ROS和MDA水平;增加SOD、GSH和GSH-PX的活性;并诱导Nrf2核转位增加。基于我们的研究结果,我们得出结论,CSO治疗通过激活Nrf2信号通路减轻缺血性脑卒中损伤诱导的氧化应激,突出了CSO作为缺血性脑卒中治疗药物的潜力。