脑创伤后bcl-2蛋白的神经保护作用

Protective Effect of bcl-2Protein on Neurons following Experimental Traumatic Brain Injury in Rats

目的探讨液压脑损伤后凋亡抑制基因bcl-2的变化规律及bcl-2基因在创伤性脑损伤后细胞凋亡中的作用。方法应用免疫组化观察大鼠中型液压脑损伤伤前及伤后6h、12h、1d、3d、7dbcl-2蛋白表达情况,应用TUNEL和电镜观察伤后细胞死亡的形态。结果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CA1、CA3及齿状回的神经元和神经胶质细胞,以海马CA3区最为显著。在高倍镜下,表达Bcl-2蛋白的神经细胞胞核形态正常,很少见到凋亡或坏死的形态特征。伤后早期(6h),打击侧海马CA3区Bcl-2蛋白表达显著下降;Bcl-2早期改变出现在伤后6h,比细胞凋亡提前表现;伤后1～3h,Bcl-2的表达下降相对缓慢。结论bcl-2蛋白在抑制脑创伤后细胞凋亡中起重要作用,bcl-2可能是一种可诱导的神经保护因子。

Objective To investigate the change in bcl-2,a gene inhibiting apoptosis and its role in neuronal apoptosis following traumatic brain injury(TBI).Method Male Sprague-Dawley rats were subjected to lateral fluid percussion brain injury(FPI)of moderate severity.Bcl-2protein expression in brain tissue was detected by immunohistochemistry before the FPI and6,12,24,72,148hours after FPI.The neuronal apoptosis in the brain were detected by TUNEL and election microscope.Results Bcl-2expression was observed in the cerebral cortex,subcortical white matter,dentate gyrus,and hippocampal CA1and CA3ipsilateral to injured hemisphere.Bcl-2positive neurons displayed normal nuclei morphology;The morphological features of apoptosis or necrosis in few Bcl-2positive neurons were observed.The immunoreactivity of Bcl-2protein decreased significantly in the hippocampus ipsilateral to the impacted site as early as6h after the TBI as compared with that before the TBI.The decrease in bcl-2protein expression became relatively slow from1to3hours after TBI.Conclusion Bcl-2may play an important role in inhibiting apoptosis after TBI and may be an inducible factor protecting the neurons in the CNS.