一氧化氮合酶抑制剂对缺血性海马迟发性神经元死亡的保护作用

Protective effects of nitric oxide synthase inhibitor on ischemia induced hippocampal delayed neuronal death

目的 :研究一氧化氮 ( NO)在缺血性海马迟发性神经元死亡 ( DND)中的作用 ,观察非选择性一氧化氮合酶 ( nitricoxidesynthase,NOS)抑制剂 NG-nitro-L-arginine( L-NNA)对缺血性海马 DND的影响。方法 :实验分为假手术组、生理盐水治疗组、L-NNA治疗组。采用大鼠 4血管关闭方法制作了全脑缺血再灌流模型 ,以假手术组为对照 ,检测了脑缺血 1 0 min再灌流 72 h海马区 NOS活性的变化并观察计量了海马 CA1 区组织病理改变 ;同时观察了 L-NNA对海马区 NOS活性和 CA1 区病理改变的影响。结果 :生理盐水治疗组海马组织 NOS活性显著升高( P<0 .0 1 ) ,L-NNA可部分抑制海马区 NOS活性 ( P<0 .0 1 ) ,使海马 CA1 区神经元存活数显著增加 ( P<0 .0 1 )。结论 :NO在海马 CA1 区 DND发生中具有毒性作用 ,L-NNA对海马 CA1 区神经元损伤有一定的保护作用。

Objective: To study the role of nitric oxide (NO) in hippocampal delayed neuronal death (DND) after transient global ischemia and observe the effects of nonselective nitric oxide synthase (NOS) inhibitor N G nitro L arginine(L NNA)on DND.Methods: Mature Wistar rats were randomly seperated into Sham operated control group,Saline treated group,L NNA group.The model of reperfusion following cerebral global ischemia for 10 min to produce neuronal death was made by 4Vo with Wistar rats.Histological survey was carried out at 72 hours after reperfusion following 10 min ischemia by hematoxylin eosin staining by quantitative pathology,at the same time,the activity of NOS in hippocampus was assessed.The effect of L NNA on DND was observed simultaneously.Results: The activity of NOS in hippocampus of saline treated groups was significantly higher than that of sham operated control group.L NNA could not only restrain the activity of NOS,but also protect against the neuronal death in the CA 1 layer.Conclusions: NO played an important role in the pathogenesis of DND in the CA 1 layer of the hippocampus after brief ischemia. Furthermore,repetitive intraperitoneally administration of L NNA had a protective effect of DND.