环氧合酶-1基因缺失阻断褪黑素对脑缺血的保护作用

目的探讨褪黑素对脑缺血的保护作用及环氧合酶-1(CPX-1)在其中的作用。方法应用光化学法对野生型及COX-1基因缺失纯合型小鼠诱导脑梗死,给予褪黑素(15 mg/kg)及0．9%氯化钠溶液进行治疗。术后第3 d应用TTC染色测量脑梗死体积,应用尼氏染色分别对缺血半暗带区存活神经元进行定量分析。结果(1)COX -1基因对脑梗死体积和缺血半暗带区神经元数目无影响;(2)褪黑素减小野生型小鼠组的脑梗死体积,增加海马区缺血半暗带内的神经元数目,但是对COX-1基因缺失的纯合型小鼠的脑梗死体积和缺血半暗带区的神经元数目无影响;(3)褪黑素治疗与COX-1基因对总梗死体积、皮层梗死体积和海马区缺血半暗带神经元数目有显著的交互影响。结论COX-1基因对光化学法所致的脑缺血无影响。褪黑素对野生型小鼠的脑保护作用随着COX-1基因缺失而消失,其神经保护作用通过或部分通过抑制COX-1实现。

Neuroprotective Effect of Melatonin on Cerebral Ischemia is Inhibited by Cyclooxygenase-1 Gene Knockout

Objective To investigate the effect of melatonin on cerebral ischemia,and the role of cyclooxygenase-1 (COX-1)in the neuroprotective mechanism.Methods Photothrombotic stroke was induced in COX-1 gene wild-type and homozygous knockout mice with vehicle or melatonin(15 mg/kg)administration.On the third d after cerebral ischemia,infarct volume was measured with TFC method,and the amount of the survival neuron in the penumbra was counted using Nissl staining. Results(1)COX-1 gene had no effect on the cerebral infarct volume and the amount of survival neuron in the penumbral. (2)Melatonin decreased the cerebral infarct volume and increased the amount of survival neuron over the penumbra in hippocam- pus in COX-1 gene wild type mice,whereas had no effect in the COX-1 gene homozygous knockout mice.(3)Melatonin and COX-1 gene had interaction effect on the cerebral infarct volume and the amount of survival neuron over the penumbra in hippo- campus.Conclusion COX-1 gene does not alter susceptibility to photothrombotic stroke.Systemic administration of melatonin protects the brain from photothrombotic stroke in the COX-1 gene wild-type mice,but not in the COX-1 gene homozygous knockout mice.It appears that neuroprotection of melatonin may be mediated or partially mediated by inhibition of COX-1.