头部X射线照射致认知障碍过程中小鼠海马小胶质细胞形态变化

Relationship between cognitive impairment induced by local radiation and morphological changes of hippocampal microglia

探讨小胶质细胞在头部X射线照射所致认知障碍过程中的作用。18只ICR(Institute ofCancer Research)小鼠随机分为对照组和头部辐照组,头部辐照组小鼠接受X射线单次头部辐照至吸收剂量10 Gy。辐照56 d后分别采用新旧事物识别实验和新旧位置识别实验检测小鼠认知功能;免疫组织化学法检测小鼠海马小胶质细胞标记物IBA-1阳性细胞数目变化;Sholl Analysis定量分析小胶质细胞形态变化;RT-PCR检测海马M1/M2型小胶质细胞标记物(CD16、INOS、CD68、CXCL10、Arg1、CD206)mRNA水平表达变化。结果显示:与对照组相比,头部辐照组小鼠新事物时间辨别指数(p<0.01)和新位置时间辨别指数(p<0.05)均明显降低;小鼠海马齿状回区(Dentate gyrus,DG)IBA-1阳性细胞数明显增加(p<0.05);小胶质细胞体变大,突起回缩,树突分支数与同心圆交点数目减少(p<0.05);小鼠海马M1型小胶质细胞标记物CD68表达上调(p<0.05),M2型小胶质细胞标记物Arg1表达下调(p<0.001)。头部X射线照射致认知障碍可能与小鼠海马小胶质细胞形态变化及小胶质细胞向M1型极化相关。

To investigate the role of microglia in the process of cognitive impairment caused by local ionizing radiation,eighteen male mice from the institute of cancer research(ICR)were randomly divided into a control group(Control)and a head 10 Gy irradiation group(Irradiation,10 Gy-IR).The head ionization irradiation group underwent X-ray(Siemens linear accelerator)single head irradiation illuminated to an absorbed dose of 10 Gy.Fifty-six days later,the new and old object recognition test and the new and old place recognition test were used to test the cognitive function of the mice;immunohistochemistry was used to detect the mouse hippocampal microglia marke(IBA-1)change;RT-PCR was used to detect changes at the mRNA level of hippocampal M 1/M 2 microglia markers(CD 16,INOS,CD 68,CXCL 10,Arg 1,CD 206).The results showed that compared with the control group,the time discrimination index of new things(p<0.01)and the time discrimination index of new positions(p<0.05)of mice in the head ionization irradiation group were significantly reduced.The number of IBA-1 positive cells in the dentate gyrus(DG area)of the mouse hippocampus increased significantly(p<0.05).The microglia in the hippocampal dentate gyrus of mice in the head ionization irradiation group increased in size.The protrusion retracted and the number of dendritic branches and the number of intersections of concentric circles decreased significantly(p<0.05).The expression of M 1-type microglia marker CD 68 in the hippocampi of mice irradiated with the head was significantly upregulated(p<0.05),whereas the expression of M 2-type microglia marker Arg 1 was significantly downregulated(p<0.001).It is suggested that the cognitive impairment in mice caused by head X-ray irradiation may be related to the morphological changes in hippocampal microglia.