Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte
Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte
复制标题
棉籽油通过抑制小胶质细胞和星形胶质细胞的炎症激活减轻缺血性中风损伤
DOI：
10.1186/s12974-020-01946-7
复制
发表时间：
2020-09-11
影响因子：
9.3
通讯作者：
Ma, Yulong
中科院分区：
文献类型：
--
作者：
Liu, Min;Xu, Zhipeng;Ma, Yulong
背景缺血性脑卒中是全球第二大死亡原因。有效溶栓治疗的时间窗较窄，促使人们寻找替代预防策略。小胶质细胞和星形胶质细胞激活介导的炎症在缺血性卒中损伤中起关键作用。棉籽油（CSO）已被证明对外周组织损伤具有抗炎作用，尽管CSO主要用作脂溶性药物的溶剂。然而，CSO在神经保护中的作用，对中风还没有以前reported.MethodsWe治疗成年雄性大鼠CSO（1.3 ml/kg，皮下注射，隔日一次，持续3周），然后构建一个大脑中动脉闭塞（MCAO）模型，随后再灌注24 h。然后，我们测量了神经功能评分、梗死体积、神经元损伤和脑水肿;我们还测量了促炎细胞因子的水平，（IL-1β、IL-6、TNF-α）、小胶质细胞和星形胶质细胞活化程度、Toll样受体4（TLR 4）、核因子κ B（NF-κB）、C3 d和S100 A10的蛋白表达水平，结果CSO治疗组神经功能缺损明显改善，梗死体积缩小，神经元损伤、血脑屏障（BBB）破坏和脑水肿减轻。此外，CSO处理显著减少小胶质细胞和星形胶质细胞活化，抑制TLR 4和NF-κB蛋白表达，并减少IL-1β、IL-6和TNF-α的释放。最后，CSO治疗显著降低C3 d/胶质细胞酸性蛋白（GFAP）阳性细胞数和C3 d蛋白表达，增加S100 A10/GFAP阳性细胞数和S100 A10蛋白表达。CSO可能通过抑制TLR 4/NF-κB通路，减少A1表型神经毒性星形胶质细胞的活化，成为预防缺血性脑卒中的新策略。
BackgroundIschemic stroke is the second leading cause of death globally. The narrow time window for administering effective thrombolytic therapy motivates the search for alternative prevention strategies. Microglia and astrocyte activation-mediated inflammation play a pivotal role in ischemic stroke injury. Cottonseed oil (CSO) has been shown to exert anti-inflammatory effects against peripheral tissue injury, although CSO is mostly used as a solvent for lipid-soluble drugs. However, the role of CSO in neuroprotection against stroke has not been previously reported.MethodsWe treated adult male rats with CSO (1.3 ml/kg, subcutaneous injection, once every other day for 3 weeks) and then constructed a middle cerebral artery occlusion (MCAO) model followed by 24 h of reperfusion. Then, we measured the neurological scores, infarction volume, neuronal injury, and brain edema; we also measured the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), degree of microglial and astrocytic activation, protein expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), C3d and S100A10, and the presence of A1 type astrocytes and A2 type astrocytes.ResultsWe found that CSO treatment significantly improved the neurological deficit, reduced infarction volume, and alleviated neuronal injuries, blood–brain barrier (BBB) disruption, and brain edema. Additionally, CSO treatment significantly reduced microglial and astrocytic activation, inhibited TLR4 and NF-κB protein expression, and reduced the release of IL-1β, IL-6, and TNF-α. Finally, CSO treatment significantly decreased the number of C3d/glial fibrillary acidic protein (GFAP)-positive cells and C3d protein expression, and increased the number of S100A10/GFAP-positive cells and S100A10 protein expression.ConclusionOur results first found that CSO treatment alleviated ischemic stroke injury by reducing microglial and astrocytic activation and inflammation, which was related to the inhibition of TLR4/NF-κB pathway and the reduction of A1 phenotype neurotoxic astrocyte activation, suggesting that CSO could be a new strategy in the prevention of ischemic stroke.