5-脂氧合酶抑制剂zileuton对大鼠局灶性脑缺血/再灌注损伤的保护作用

Protective effect of 5-lipoxygenase inhibitor zileuton on focal cerebral ischemia-reperfusion injury in rats

目的观察5-脂氧合酶抑制剂zileuton对大鼠局灶性脑缺血/再灌注损伤的保护作用。方法线栓法阻塞大鼠大脑中动脉2 h/再灌注24 h,观察zileuton 10、50 mg.kg-1对脑梗塞体积、脑组织髓过氧化物酶(MPO)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)、一氧化氮(NO)、一氧化氮合酶(NOS)含量的影响。结果zileuton 10、50 mg.kg-1均能明显缩小脑梗死灶,降低NOS活性及NO含量,高剂量组亦可降低脑组织MDA含量、增加GSH-PX活性、缓解MPO升高。结论zileuton对大鼠局灶性脑缺血/再灌注损伤有保护作用。

Aim To investigate the protective effect of zileuton, a 5-1ipoxygenase inhibitor, on focal cerebral ischemia-reperfusion injury in rats. Methods The right middle cerebral artery of the rat was occluded by inserting a thread through internal carotid artery for 2 h,and then reperfused for 24 h. Zileuton（ 10,50 mg ·kg^-1 ） was orally administered 2 h before ischemia and 0,5,10 h after reperfusion. After 24 h reperfusion, the content of malondialdehyde （ MDA ） and nitric oxide （NO） , the activities of glutathion peroxidase （ GSH- PX）, myeloperoxidase（MPO） and nitricoxide synthase （NOS） were measured. Results Compared with vehicle group, the infarct size,content of NO and NOS of the brain were significantly reduced in 10 and 50 mg · kg^-1 zileuton groups; zileuton 50 mg·kg ^-1 also reduced the content of MDA, increased the activity of GSH-PX, and inhibited the increase of MPO in brain tissue. Conclusion Zileuton possesses the neuroprotective effects on focal cerebral ischemia-reperfusion injury in rats.