L-NIL在大鼠创伤性脑损伤中的应用研究

Research of selective inducible nitric oxide synthase inhibitator L-NIL on rats after traumatic brain injury

目的 探讨选择性诱导型一氧化氮合酶 (iNOS)抑制剂L N6 亚氨乙基 赖氨酸 (L NIL)在大鼠创伤性脑损伤 (TBI)模型中对大鼠伤后学习记忆功能、海马神经元的影响。方法 2 4只SD大鼠随机分为假创伤性脑损伤组、创伤性脑损伤组、非选择性一氧化氮合酶 (NOS)抑制剂N 硝基 L 精氨酸 (L NNA)组、选择性诱导型一氧化氮合酶抑制剂L NIL组。其中L NNA组、L NIL组分别于伤后即刻、2 4h、4 8h经腹腔注射L NNA或L NIL。进行避暗回避试验以评价伤后各组大鼠的学习记忆功能恢复情况。伤后第 7d处死大鼠取脑 ,采用Nissl染色及神经元抗核抗体 (NeuN)免疫组化染色观察测量伤侧海马CA2区锥体细胞层面积。结果 ①L NIL组避暗回避试验结果显著好于创伤性脑损伤组 (P <0 .0 5 )。②L NIL组海马CA2区锥体细胞层面积与创伤性脑损伤组比较显著增加 (P<0 .0 5 )。③L NIL组避暗回避试验结果及海马CA2区锥体细胞层面积值均优于L NNA组。结论 适当地应用选择性iNOS抑制剂L NIL可促进大鼠脑损伤后学习记忆功能的恢复 ,保护海马神经元 。

Objective To observe the effect of the selective inducible nitric oxide synthase inhibitator L-N 6-(1-Iminoethyl)lysine (L-NIL) on learning and memory of rats after traumatic brain injury (TBI).Methods Twenty-four SD rats were randomly divided into four groups: shame group, controlled group, L-NNA group and L-NIL group. The dark avoidance task was done to evaluate the recovery of the neurological function of learning and memory after TBI. The rats were executed in the seventh day after TBI , the brain frozen sections were stained by Nissl stain and neuronal nuclei antibody (NeuN) immunohistochemical stain to explore and to measure the area of cells in the hippocampal CA2 zone.Results ①The outcome of dark avoidance task of L-NIL group was better than that of control group. ②The hippocampal CA2 area of L-NIL group significantly increased compared to the control group. ③The outcome of dark avoidance task and hippocampal CA2 area of L-NIL group were better than those in L-NNA group.Conclusion The proper using of selective iNOS inhibitator can improve the neurological function of learning and memory and decrease the cells death in hippocampal CA2 zone after TBI. The effect of selective iNOS inhibitator was better than that of non-selective NOS inhibitator used in TBI.