中文摘要：

目的：在体外培养大鼠皮层神经元缺血性损伤模型中探讨两种半胱氨酰白三烯受体（CysLT1R和CysLT2R）拮抗剂——孟鲁司特和HAMI 3379的抗氧化作用.方法：以CysLT1R拮抗剂孟鲁司特和CysLT2R拮抗剂HAMI 3379预处理后,对大鼠皮层神经元进行缺糖缺氧/恢复或过氧化氢处理,观察神经元活性氧产生、线粒体膜电位、神经元存活率变化以及两种药物的作用.同时,以RNA干扰抑制CysLT1R和CysLT2R表达,观察以上变化.结果：缺糖缺氧处理1h后神经元活性氧产生增加（270.0％±6.8％,P＜0.01）,在缺糖缺氧恢复30 min时达高峰（356.0％±17.4％,P＜0.01）;0.01 ～1 μmol/L孟鲁司特和HAMI 3379均能轻度抑制缺糖缺氧及恢复诱导的活性氧产生（均P＜0.05）.缺糖缺氧及恢复诱导神经元线粒体膜电位下降,0.01～1μmol/L孟鲁司特一定程度抑制该作用（P＜0.05）,而HAMI 3379无明显作用.外源性活性氧过氧化氢呈浓度和时间依赖性损伤神经元,0.1～1 μmol/L的孟鲁司特和0.001～0.1μmol/L的HAMI 3379能轻度减轻过氧化氢诱导的损伤（均P ＜0.05）.CysLT1R小分子干扰RNA和CysLT2R短发卡RNA对以上反应均无显著影响.结论：孟鲁司特和HAMI 3379在神经元缺血性损伤中均有轻度抗氧化作用,且此作用可能不依赖受体.

英文摘要：

Objective：To investigate the antioxidative effects of two cysteinyl leukotriene receptors antagonists （CysLT1R and CysLT2R） montelukast and HAMI 3379 on ischemic injury of rat cortical neurons in vitro.Methods：Cultured rat cortical neurons were pretreated with CysLT1R antagonist montelukast and CysLT2R antagonist HAMI 3379,and then exposed to oxygen-glucose deprivation/recovery （OGD/R） or H2O2.Reactive oxygen species （ROS）,mitochondrial membrane potential （MMP） depolarization,neuronal viability and lactate dehydrogenase （LDH） release were determined.Meanwhile,RNA interference was used to inhibit the expression of CysLT1R and CysLT2R,and the effects were observed.Results：ROS production in neurons was significantly increased after 1 h OGD,which reached the peak at 30 min and lasted for 1.5 h after recovery.Montelukast and HAMI 3379 at 0.01-1 μmol/L moderately decreased OGD/R-induced ROS production （P 〈 0.05）.Montelukast mildly attenuated OGD/R-induced MMP depolarization （P 〈 0.05）,but HAMI 3379 had no effect.H2O2 reduced neuronal viability and increased LDH release,namely inducing neuronal injury.Montelukast and HAMI 3379 at 0.1-1 μmol/L moderately attenuated H2O2-induced neuronal injury （P 〈 0.05）.However,both CysLT1R siRNA and CysLT2R shRNA did not significantly affect the responses mentioned above.Conclusion：In ischemic neuronal injury,montelukast and HAMI 3379 exert a moderate antioxidative effect,and this effect may be receptor-independent.