全脑缺血大鼠海马CA1区神经元凋亡和神经生长因子的保护作用

Neuronal apoptosis and protective effect of nerve growth factor in hippocampal CA1 region after cerebral ischemia in rats

目的 研究大鼠全脑缺血再灌注后海马CA1区P75NTR、Bcl 2、Bax表达及细胞凋亡的变化及神经生长因子 (NGF)对它们的影响 ,进一步探讨该区神经元短暂脑缺血后产生凋亡及NGF对神经元保护作用的可能机制。方法 通过四血管闭塞法建立大鼠全脑缺血 再灌注模型 ,侧脑室注射NGF ,免疫组织化学法检测P75NTR、Bcl 2、Bax表达的情况 ,TUNEL法检测神经元凋亡。结果 对照组海马CA1区无P75NTR、Bcl 2阳性染色和凋亡细胞 ,可见少量Bax表达 ,再灌注后该区Bcl 2始终阴性表达 ,Bax则表达增加 ,出现P75NTR阳性表达和细胞凋亡 ;在NGF给药组 ,再灌注后海马CA1区Bcl 2出现阳性染色 ,而Bax及P75NTR的表达则明显降低 ,细胞凋亡亦明显减少。结论 再灌注后海马CA1区P75NTR、Bax的表达增加可能是神经元产生凋亡的机制之一 ,NGF抑制脑缺血后细胞凋亡的作用可能是通过对其受体的调节 ,从而调节Bcl

Objective To investigate the mechanism underlying apoptosis and protective effect of nerve growth factor (NGF) in hippocampal CA1 region after cerebral ischemia/reperfusion. Methods Wistar rats were inflicted with four vessel occlusion for global ischemia, and those in NGF group were given intraventricular injection of NGF after ischemia. Immunohistochemistry staining was used to detect P75NTR, Bcl 2 and Bax, and TUNEL method to detect apoptosis. Results The expression of Bax was positive, while the apoptosis and the expressions of P75NTR and Bcl 2 were negative in normal control. After ischemia/reperfusion, the expression of Bcl 2 was still negative, while the expression of P75NTR and Bax increased and reached its summit in day 3. TUNEL positive neurons were seen in day 2 and reached a peak in day 3. In NGF group, the expression of Bcl 2 was increased, while the expression of Bax, P75NTR and TUNEL positive cells were obviously decreased. Conclusion These findings suggest that the increased expression of P75NTR and Bax in hippocampal CA1 region after cerebral ischemia/reperfusion may be one of the main reasons for apoptosis after ischemia. Intraventricular NGF might have protective effect on neuronal apoptosis after cerebral ischemia via regulation the expression of Bcl 2 and Bax by regulated NGF receptor.