前脑缺血再灌注海马CA1区神经元死亡与一氧化氮的关系

Association between nitric oxide and neuronal death in rat hippocampus CA1 region after transient forebrain ischemia reperfusion

目的:深入研究一氧化氮在迟发性神经元死亡的发生中的作用。方法:四血管闭塞复制大鼠前脑缺血/再灌注模型,观察不同类型一氧化氮合酶(nitric-oxidesynthase,NOS)抑制剂治疗组及对照组海马CA1区一氧化氮浓度及CA1区锥体细胞密度的变化。结果:缺血/再灌注后6h海马CA1区一氧化氮浓度犤(3.83±0.90)μmol/L犦即开始升高犤缺血前为(0.93±0.08)μmol/L犦,至3d达到高峰犤(8.99±0.90)μmol/L〗;左旋硝基精氨酸甲脂(L-NAME)能降低各时相点的一氧化氮水平,氨基胍能降低再灌注后6～24h的一氧化氮水平;但两种NOS抑制剂均不能防止再灌注后3d发生的迟发性神经元死亡,其中L-NAME加重了神经元的损害,而氨基胍可明显地减轻神经元损害,有神经保护作用。结论:前脑缺血海马CA1区的迟发性神经元死亡与缺血/再灌注后的一氧化氮水平增高有关,特别是选择性诱导性NOS的作用可能更为重要。

AIM:To deeply study the effects of nitric oxide(NO) on the delayed neuronal death in the hippoampus CA1 region. METHODS:The animal models of the forebrain ischemia/reperfusion were established with 4 vessel occlusion.The nonselective nitric oxide synthase(NOS) inhibitor and selective iNOS inhibitor were used for investigating the NO changes and neuronal density in the CA1 region of hippocampus. RESULTS:The NO level in hippocampus CA1 region was increased from (0.93±0.08)μmol/L to (3.83±0.90)μmol/L at 6 hours after ischemic reperfusion,and reached the peak[(8.99±0.90)μmol/L] at 3 days. The nonselective NOS inhibitor L NAME administration could decrease the NO level and excerbated delayed neuronal death,but selective iNOS inhibitor aminoguanidine had markedly protective effects on neurons. CONCLUSION:Increased level of NO is related with the delayed neuronal death in hippocampus CA1 region after ischemia/reperfusuion.Selective iNOS plays an important role in the delayed neuronal death in hippocampus CA1 region.