氨基胍对大鼠创伤性脑损伤的保护作用

Protective effect of aminoguanide on traumatic brain injury in rats

目的探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)对大鼠创伤性脑损伤(TBI)的神经保护作用。方法采用改进的Feeney法大鼠脑损伤模型,对生理盐水(NS)组和AG组SD大鼠于伤后6 h分别腹腔注射NS或AG,每隔24 h注射1次,连续注射3次。分别于致伤后24h、72 h1、68 h取样,采用iNOS免疫组化技术,研究大鼠TBI后iNOS的表达及其细胞定位,采用凋亡细胞原位缺口末端标记法(TUNEL),观察大鼠TBI后不同时点的神经细胞凋亡情况。结果大鼠TBI后24 h,大脑损伤区周围皮质和伤侧海马iNOS阳性表达,TUNEL阳性细胞均明显增多,伤后72 h表达最明显,伤后168 h仍有表达;注射AG后,大脑损伤区周围皮质和伤侧海马的iNOS阳性细胞和TUNEL阳性细胞均明显减少(P<0.01)。结论TBI后损伤区周围皮质和伤侧海马可出现iNOS阳性细胞高表达和神经细胞凋亡,且呈相关性变化,推测iNOS的过度表达可能参与了TBI后继发性神经细胞凋亡,使用AG能明显减少iNOS阳性细胞的表达和神经细胞的凋亡。

Objective To investigate the protective effect of induced nitric oxide synthase（iNOS） aminoguanide（AG） on the traumatic brain injury（TBI） in rats. Methods SD rat model with traumatic brain injury was established by Feeney＇s method. The rats were given AG 100mg/kg（in AG group） or normal saline（in control group） ip once a day for three days. Immunohistochemistry and TUNEL were used to determine the expression of iNOS and apoptosis-associated signals in the hippocampus and cerebral cortex at 24,72,and 168 hours after injury. Results Compared with sham controls,TUNEL positive cells and iNOS positive cells were identified as early as 24 h after TBI and reached the maximum at 72 h after TBI in the ipsilateral hippocampus and the neighbour cortex. TUNEL positive cells and iNOS positive cells after TBI were significantly less in AG group than those in normal saline group. Conclusion There are the expressions of iNOS and TUNEL after TBI in selected brain region,which might be involved in the cell apoptosis secondary to TBI. AG might have a protective effect on TBI by down-regulating the expression of iNOS and inhibiting neuron apoptosis.