一氧化氮在全脑缺血再灌注大鼠脑损害中的作用

Role of nitric oxide in cerebral ischemia reperfusion injury in rats

目的 探讨一氧化氮在全脑缺血 2 0min后再灌注大鼠脑损害中的作用。方法 雄性Wistar大鼠 84只 ,体重 (2 2 0± 2 0 )g ,随机分为对照组 (12只 )和缺血组 (72只 ) ,后者设 8、2 4、48、72、96、16 8h 6个时相点。参照Pulsinelli等的方法制作大鼠全脑缺血 2 0min再灌注模型 ,于再灌注后 8、2 4、48、72、96、16 8h活杀取血及海马组织 ,对照组施行麻醉及手术 ,但不缺血 ,观察 72h后取血及海马组织 ,测定血清NSE、海马NO含量及海马CA1区锥体神经元 (Pyramidalneuron ,PN)密度。结果 ①海马NO含量于缺血再灌注后 48h明显升高 ,72h达峰值 (与对照组比较P均 <0 .0 1) ,以后逐渐下降 (96h仍明显高于对照组水平 ,P <0 .0 5 ) ,16 8h降至接近对照组 ;②缺血组各时相点血清NSE含量均显著高于对照组 (P 均 <0 .0 1) ;③缺血组海马CA1区PN密度呈明显的逐渐减少趋势 ,自 48h后均明显低于对照组 (P均 <0 .0 1) ,再灌注后 16 8h仅为对照组水平的 2 2 .8% ;④缺血再灌注后海马NO含量与血清NSE水平的变化呈显著的线性正相关 (r =0 .90 2 2 ,P <0 .0 1)。结论 NO在全脑缺血再灌注损伤中起着重要作用 ,是引起海马CA1区锥体神经元DND发生的主要因素之一。

Objective To explore the role of nitric oxide (NO) in the brain injury in the rat model of reperfusion 20 min after cerebral ischemia. Methods Eighty four male Wistar rats (weight 220±20 g) were randomized into control group ( n =12) and ischemia group ( n =72). The rats of ischemia group were established with Pulsinelli's method and killed at the time points of 8, 24, 48, 72, 96, 168 h after reperfusion. The neuron specific enolase (NSE) level in serum, the NO content and the pyramidal neuron (PN) density of CA1 area in the hippocampus were determined respectively. Results ①The NO content in the hippocampus increased significantly at the 48th h ( P <0.01), reached a peak at the 72nd h ( P <0.01), decreased gradually from the 96th h ( P <0.05) and fell to the level of control group at the 168th h after reperfusion. ②The NSE level in serum was significantly higher in ischemia group at every time points than in control group ( P <0.01). ③The PN density in CA1 area of the hippocampus decreased in ischemia group and was significantly lower in this group than in the control ( P <0.01). It was only 22.8% of that of the control at the 168th h after reperfusion. ④In ischemia group, the NO content in the hippocampus had linear correlation with the change of the serum NSE level ( r =0.9022, P <0.01). Conclusion NO plays an important role in cerebral ischemia reperfusion and is an important factor which contributing to delayed neuronal death in CA1 area of the hippocampus.