Zileuton对脑缺血后空间学习记忆障碍的改善作用

Zileuton improves brain ischemia-induced spatial learning and memory deficits

目的观察5-脂氧酶选择性抑制剂Zileuton对全脑缺血后空间学习记忆能力的改善作用。方法以两侧颈总动脉阻断合并低血压法诱导大鼠全脑缺血模型,Zileuton 30 mg/kg灌胃给药,共7天。应用Morris水迷宫实验检测大鼠空间学习记忆能力,海马切片观察CA1神经元病理变化。结果 Morris水迷宫实验表明,全脑缺血后大鼠活动总路径和逃避潜伏期明显延长,空间学习记忆能力下降(P<0.05或P<0.01);Zileuton 30 mg/kg提高全脑缺血大鼠Morris水迷宫实验学习记忆成绩(P<0.05)。海马病理切片观察显示,全脑缺血后海马CA1神经元损伤(P<0.01),Zileuton减轻脑缺血后神经元损伤(P<0.05)。结论 5-脂氧酶抑制剂Zileuton能改善大鼠全脑缺血后空间学习记忆障碍,其机制与药物对海马CA1神经元的神经保护作用有关。

Objective： To evaluate the effect of zileuton, a selective 5-1ipoxygenase inhibitor, on spatial learning and memory following global cerebral ischemia in rats. Methods： Transient global cerebral ischemia was induced by bilateral carotid artery occlusion combined with hypotension. Zileuton （30 mg/kg） was orally administered for 7 days. Spatial learning and memory ability was measured by Morris water maze test, and CA1 neuron damage in the hippocampus was observed after ischemia. Results ： Global cerebral ischemia caused cognitive impairment（P 〈 0.05 ~ P 〈 0.01 ） and CA1 neuron injury（ P 〈 0.01 ）; 5-LOX inhibitor zileuton （30 mg/kg）significantly ameliorated spatial learning and memory deficits（P 〈 0.05）, and attenuated hippocampal CAI neuron damage after ischemia（P 〈 0.05）. Conclusion： The 5- lipoxygenase inhibitor zilenton improves ameliorates spatial learning and memory deficits after global cerebral ischemia in rats,which may be related to the neuroprotection effect of zileuton on CA1 neuron.