放线菌酮对大鼠脑损伤的神经保护作用

Neuroprotective functions of cycloheximide following traumatic brain injury in rats

目的 探讨放线菌酮对脑创伤的神经保护作用及其机制。 方法 在液压颅脑损伤模型中 ,观察伤后神经功能、神经病理学改变、细胞凋亡的特征以及凋亡促进基因bax的表达 ;比较治疗组在液压致伤前 5min皮下注射放线菌酮 (2 .5mg kg)对上述指标的影响。 结果 治疗组伤后行走功能、平衡功能障碍程度明显低于未治疗组 (P <0 .0 1)。治疗组大鼠伤后神经病理学改变减轻 ,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。伤后不同脑区bax蛋白水平升高 ,放线菌酮可抑制bax蛋白表达。 结论 放线菌酮能有效地抑制脑创伤后bax蛋白表达及神经细胞凋亡 ,减轻神经病理损害 。

Objective To investigate the neuroprotective functions and the molecular mechanisms of cycloheximide (CHX) following traumatic brain injury (TBI). Methods Male SD rats were subjected to lateral fluid percussion brain injury (FPI) of moderate severity. CHX (2.5 mg/kg) was administered subcutaneously 5 minutes before TBI. 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 internucleosomal DNA fragmentation of apoptosis was demonstrated by DNA gel electrophoresis. The up-regulation of bax expression was also observed. Results The scores of beam walk test and 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 ipsilateral to the injured hemisphere at various time points following TBI. No DNA ladder was detected in the treated rats. During 1 3 days after injury, the bax protein expression increased significantly. Bax expression was observed in the cerebral cortex, subcortical white matter, dentate gyrus, and hippocampal CA1 and CA3 region ipsilateral to injured hemisphere. In the CHX treated groups, the bax expression was halted. Conclusions CHX may block the up regulation of bax expression, inhibit cell apoptosis, mitigate the neuronal damage and has a protective function on the neurons.