5-脂氧合酶抑制剂齐留通对N-甲基-D-门冬氨酸诱导的小鼠脑损伤的保护作用

Protective Effects of 5-lipoxygenase Inhibitor Zileuton on Brain Injury Induced by N-methyl-D-aspartate in Mice

[目的]观察5-脂氧合酶(5-LOX)抑制剂齐留通对N-甲基-D-门冬氨酸(NMDA)皮层注射诱导的小鼠脑损伤的影响。[方法]NMDA(100 nmoL)皮层直接注射建立脑损伤模型,用干湿重法评价脑水肿,脑切片TTC染色检测梗死体积,甲苯胺蓝染色法评价神经元的损伤。以NMDA拮抗剂氯胺酮(30mg.kg-1)为阳性对照药,3、10、30 mg.kg-1齐留通在NMDA皮层注射前30 min腹腔注射给药1次,NMDA注射后24 h评价上述指标。[结果]干湿重法显示皮层注射NMDA并未引起脑水含量的变化,齐留通对脑水含量没有影响;NMDA(100nmoL)皮层注射能诱导大面积脑梗死,中、高剂量的齐留通(10、30mg.kg-1)和氯胺酮(30 mg.kg-1)能明显降低梗死灶体积;NMDA诱导神经元变性,中、高剂量的齐留通和氯胺酮减轻神经元变性,增加损伤区神经元数量。[结论]5-LOX抑制剂齐留通对NMDA皮层注射诱导的小鼠脑损伤有保护作用。

[Aim] To detemline whether zileuton, a 5-lipoxgenase（S-LOX） inhibitor, has an effect on N-methyl-D-aspartate（NM1）A）-induced brain injury in mice. [Methods] Brain injury was induced by direct microinjection of NMDA （100 nmol ） into the cerebral cortex. The brain edema was assessed by dry and water weight; The lesion volume was assessed by TTC stasining; The neuron injury was assessed by toluidine blue staining. Zileuton （3,10 and 30 mg/kg） and ketamine （30 mg/kg）, a NMDA antagonist, were intraperitoneally injected 30min before NMDA injection. At 24 h after NMDA microinjection, the above-mentioned indexes were performed. [Results] NMDA microinjection did not induce the changes of brain water content by dry and wet weight assay. Ziuleuton had not effect on brain water content; NMDA microinjection produced well-defin＇ed focal lesions. Zileuton （10,30 mg/kg） and ketamine（30 mg/kg） decreased the total lesion volume induced by NMDA; In addtion, NMDA microinjection also induced neuron degeneration. Zileuton （10,30mg/kg）and ketamine （30mg/kg）ameliorated neuron degeneration and increased neuron density in injuried area. [Conclusion] Zileuton, a 5-Lox inhibitor, has a protective effect on NMDA-induced brain injury in mice .