p75NTR在颅脑放疗后海马神经发生损伤中的作用

The role of p75 neurotrophin receptor in hippocampal neurogenesis impairment after cranial irradiation

目的探讨p75神经营养因子受体（p75 neurotrophin receptor，p75NTR）在电离辐射所致海马神经发生损伤中的作用。方法30只Sprague。Dawley大鼠接受单次10Gy4MeV电子线全脑照射。于照射后1个月取大鼠海马组织，应用蛋白印记法检测p75NTR蛋白表达水平变化，应用免疫荧光激光共聚焦方法检测海马区神经发生变化情况。通过立体定向方法海马内注射AAV—shp75NTR特异性敲除p75NTR，分析p75NTR与神经发生的关系。结果蛋白印记法结果显示p75NTR蛋白表达在照射后升高43．8％（P〈0．05）。免疫荧光染色显示照射后1个月大鼠BrdU＋NeuN＋细胞数较对照组相比下降81．5％（P〈0．01），而在特异性敲除p75NTR后，海马区神经发生得到了明显保护。结论D75NTR在电离辐射所致海马神经发生损害过程中具有重要作用。

Objective To investigate the role of p75 neurotrophin receptor （p75NTR） in the irradiation-induced hippocampal neurogenesis impairment. Methods Thirty Sprague-Dawley rats were subject to whole brain irradiation with a single dose of 10 Gy 4 MeV electron beam. At 1 month after irradiation, the hippocampal tissues of the rats were collected. Western blot was used to detect the changes in the expression level of p75NTR protein. Immunofluoreseence confocal laser microscopy was performed to observe the variations in the hippoeampal neurogenesis. The stereotatic method was adopted for intra- hippocampal injection of AAV-shp75NTR to specifically knock out p75NTR. The relationship between p75NTR and hippocampal neurogenesis was analyzed. Results Western blot demonstrated that the expression of p75NTR protein was significantly up-regulated by 43.8% after irradiation （P〈 0. 05 ）. Immunofluorescent staining showed that the quantity of BrdU ＋NeuN ＋ cells in rats was significantly decreased by 81.5% at 1 month after irradiation compared with that in the control group （P〈0. 01 ）.After the specific knockout of p75NTR, hippocampal neurogenesis was obviously protected. Conclusion p75NTR plays a pivotal role in the irradiation-induced hippocampal neurogenesis impairment.