摘要
目的 探讨脂质过氧化反应与脑损伤后细胞凋亡及bcl- 2基因表达的关系。 方法 在大鼠液压颅脑损伤模型中 ,观察其运动神经功能 ;脑创伤后细胞凋亡的形态和生化特征 ;伤后bcl- 2基因表达情况 ;比较伤前给予U - 74389G对上述指标的影响。 结果 治疗组的颅脑伤大鼠伤后行走功能、平衡功能障碍程度明显低于未治疗组 (P <0 .0 1)。治疗组大鼠不同脑区各个时间点凋亡细胞数均显著减少 ,DNA电泳未见凋亡带谱。Bcl- 2免疫反应阳性细胞主要位于伤侧大脑半球皮质、皮层下白质、海马及齿状回的神经细胞。表达Bcl- 2蛋白的神经细胞很少见到凋亡或坏死的形态特征。Bcl- 2早期改变出现在伤后 6h ,比细胞凋亡出现早。注射U - 74389G能阻止bcl- 2蛋白下调。 结论 U - 74389G能阻止大鼠液压脑损伤后bcl- 2基因表达下调 ,抑制脑创伤所致细胞凋亡 。
Objective To investigate the relationship of oxidative stress with apoptosis and bcl 2 expression following traumatic brain injury (TBI). Methods Male SD rats were subjected to lateral fluid percussion brain injury (FPI) of moderate severity. U 74389G (20 mg/kg) was administered intravenously before FPI. The neurological functions were estimated by beam walk test and beam balance test. In addition to morphological evidence of apoptosis, TUNEL histochemistry was used to identify DNA fragmentation in situ at both light and electron microscopic levels. Whereas characteristic of internucleosomal DNA fragmentation of apoptosis was demonstrated by DNA gel electrophoresis. Bcl 2 protein expression was detected by immunohistochemistry. Results The scores of beam walk test and the beam balance test were significantly improved ( P <0.01) in the treated animals. The treatment significantly reduced the number of apoptotic cells that we counted in the areas from ipsilateral to the injured hemisphere at various time points following TBI. No DNA ladder was detected in the treated rats. Bcl 2 expression was observed in the cerebral cortex, subcortical white matter, dentate gyrus, and hippocampal CA1 and CA3 region ipsilateral to injured hemisphere. Bcl 2 positive cells displayed normal nuclear morphology. Little Bcl 2 positive cells revealed morphological feature of apoptosis or necrosis. The immunoreactivity of Bcl 2 protein decreased significantly in the hippocampus ipsilateral impact site as early as 6 hours after injury. In the U 74389G treated groups, the down-regulation of bcl 2 expression was halted. Conclusions U 74389G may block oxidative stress and halt the down-regulation of bcl 2 expression. These may be one of the molecular mechanisms of the neuroprotective effects by U 74389G.
出处
《中华创伤杂志》
CAS
CSCD
北大核心
2001年第6期356-358,共3页
Chinese Journal of Trauma
基金
军队"九五"指令性课题基金资助项目 ( 96L0 36)
