Acute ischemic stroke (AIS) is a serious cardiovascular and cerebrovascular disease; Oxidative stress and neuroinflammation are important factors which destroy blood-brain barrier (BBB) in AIS. In the study, a series of 1,3,5-triphenyl-1,2,4-triazole derivatives were designed and synthesized; the optimal compound 9 was obtained by screening their anti-oxidant and anti-inflammatory effects; the neuroprotection effect of compound 9 was evaluated with a rat middle cerebral artery occlusion (MCAO) model. Subsequently, the mechanism of neuroprotection were explored via Western blot. The results prompt compound 9 maybe exert anti-AIS neuroprotection by inhibiting oxidative stress and neuroinflammation inhibition by inhibiting Keap1, COX-2 and iNOS. At the same time, it can protect BBB by reducing glycocalyx degradation and matrix metallopeptidase-9 levels. Its LD₅₀ > 1000 mg/kg on mice and hERG channel inhibition IC₅₀ > 30 μM, which lower acute toxicity and hERG channel inhibition would make compound 9 a promising stroke treatment candidate.

急性缺血性脑卒中（AIS）是一种严重的心脑血管疾病；氧化应激和神经炎症是破坏AIS血脑屏障(BBB)的重要因素。本研究设计并合成了一系列1,3,5-三苯基-1,2,4-三唑衍生物；筛选其抗氧化、抗炎作用，得到最优化合物9 ；用大鼠大脑中动脉闭塞(MCAO)模型评价化合物9的神经保护作用。随后，通过蛋白质印迹探索神经保护机制。结果提示化合物9可能通过抑制氧化应激发挥抗AIS神经保护作用，并通过抑制Keap1、COX-2和iNOS发挥抗神经炎症抑制作用。同时，它可以通过减少糖萼降解和基质金属肽酶 9 水平来保护 BBB。其对小鼠的 LD ₅₀  > 1000 mg/kg 和 hERG 通道抑制 IC ₅₀  > 30 μM，降低了急性毒性和 hERG 通道抑制，这使得化合物9成为有前途的中风治疗候选药物。