CysLT1受体拮抗剂montelukast对全脑缺血海马神经元损伤的保护作用

目的 观察全脑缺血后海马神经元损伤及半胱氨酰白三烯1( cysteinyl leukotriene 1,CysLT1)受体表达变化,评价CysLT1受体选择性拮抗剂montelukast对全脑缺血海马神经元损伤的保护作用.方法 两侧颈总动脉阻断结合降压药诱导大鼠全脑缺血模型,海马切片检查CA1神经元病理改变.免疫组化染色观察CysLT1受体的表达变化,montelukast缺血前后多剂量灌胃给药,评价其对全缺血后CA1神经元损伤的影响.结果 全脑缺血后2～3d,海马CA1区神经元损伤、CysLT1受体表达上调,Montelukast(0.5和1.0 mg/kg)剂量依赖性地减轻全脑缺血后海马神经元损伤(P＜0.05和P＜0.01);montelukast(0.5 mg/kg,连续给药5d)在缺血后30 d对CA1神经元损伤仍有保护作用(P＜0.05).结论 CysLT1受体参与全脑缺血后海马神经元损伤,CysLTt受体拮抗剂montelukast对全脑缺血CA1神经元损伤有剂量依赖性和长期的保护作用.

Effect of CysLT1 Receptor Antagonist Montelukast on Hippocampal Neuronal Damage after Global Ischemia in Rats

Objective To observe the changes of cysteinyl leukotriene 1(CysLT1) receptor expression in global ischemic injury and evaluate the effect of montelukast,a CysLT1 receptor selective antagonist,on hippocampal neuronal damage after global ischemia in rats.Methods Global ischemia was induced by bilateral common carotid artery occlusion combined with hypotension in rats.CysLT1 receptor expression was detected by immunohistochemistry.Montelukast was orally administered before and after ischemia.The number of living CA1 neurons was assessed.Results CysLT1 receptor expression was up-regulated in the ischemic hippocampus after global cerebral ischemia.Treatments with concerned doses of montelukast(0.5 and 1.0 mg/kg) significantly attenuated the damage of CA1 neurons in a dose-dependent manner.Furthermore,a protective effect of montelukast(0.5 mg/kg,5 consecutive days) from hippocampal neuronal damage lasted for 30 days after ischemia,suggesting montelukast has a long-term neuroprotection function.Conclusion CysLT1 receptor exacerbates in the damage of hippocampal neurons after global cerebral ischemia.Montelukast has a long-term neuroprotective effect in a dose-dependent manner on hippocampal neuronal damages following global ischemia in rats.