Ischemic stroke is the third most common cause of death and the leading cause of disability worldwide in adults. The antiepileptic drug valproic acid (VPA) was reported to protect cerebral ischemia/reperfusion injury. However, the action mechanism of VPA in cerebral ischemia/reperfusion injury has not been fully understood. We explored the action mechanism of VPA in vivo and in vitro. Gerbils were subjected to transient global cerebral ischemic-reperfusion injury, and hippocampal neuron injury was treated with oxygen-glucose deprivation in vitro. Morris water maze test was performed to evaluate the cognitive dysfunction. Histopathological examinations and western blot were performed to evaluate the pyroptosis of neurons. The results showed that VPA attenuated the cognitive dysfunction, pyroptosis of the gerbils suffer from ischemic-reperfusion injury and decreased hippocampal neurons pyroptosis induced by oxygen-glucose deprivation in vitro. In addition, western blot and real-time PCR analysis revealed that VPA modulated the protein expression of apoptosis repressor with caspase recruitment domain (ARC), caspase-1 and IL-1β/IL-18. Our results suggested that VPA alleviated ischemic/reperfusion injury-mediated neuronal impairment by anti-pyroptotic effects.

中文翻译：

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丙戊酸通过抗化脓性途径减轻沙鼠的整体脑缺血/再灌注损伤。

缺血性中风是全球第三大最常见的死亡原因和致残的主要原因。据报道，抗癫痫药丙戊酸（VPA）可保护脑缺血/再灌注损伤。但是，尚未完全了解VPA在脑缺血/再灌注损伤中的作用机制。我们探讨了VPA在体内和体外的作用机理。对沙鼠进行短暂的整体性脑缺血再灌注损伤，并在体外用氧葡萄糖剥夺治疗海马神经元损伤。进行莫里斯水迷宫测试以评估认知功能障碍。进行组织病理学检查和蛋白质印迹以评估神经元的发烧。结果表明，VPA减轻了认知功能障碍，沙鼠的热凋亡受到缺血-再灌注损伤，并在体外因缺氧-葡萄糖剥夺而引起的海马神经元热凋亡减少。此外，蛋白质印迹和实时PCR分析显示，VPA可以通过caspase募集域（ARC），caspase-1和IL-1β/ IL-18调节凋亡抑制因子的蛋白表达。我们的结果表明，VPA通过抗化脓作用减轻了缺血/再灌注损伤介导的神经元损伤。