纳米银联合辐射后脑胶质瘤细胞凋亡与小胶质细胞的变化及其关系

摘要

目的：研究纳米银联合辐射后大鼠脑胶质瘤细胞凋亡与瘤内小胶质细胞的变化及其关系。方法：将C6细胞立体定向接种于大鼠右侧尾状核，建模后第8天将荷瘤鼠随机分成辐射对照组和纳米银联合辐射组，分别立体定向注入等体积的去离子水及20μg的纳米银，并行单次电离辐射。应用原位末端转移酶标记（ TUNEL）法和OX42免疫组织化学染色分别检测辐射后瘤组织内细胞凋亡及小胶质细胞活性的动态变化。结果：TUNEL阳性细胞数目在辐射后6 h显著增加，24 h明显减少；辐射后6 h胶质瘤内小胶质细胞开始激活，随着时间的延长活性进一步增强。辐射后6 h 和24 h，纳米银联合辐射组TUNEL阳性细胞数目和小胶质细胞活性均较辐射对照组增加，差异有统计学意义（ P＜0.001）。小胶质细胞活化与胶质瘤细胞凋亡的变化趋势不同，前者迟于后者。结论：纳米银联合辐射后胶质瘤细胞凋亡增加，小胶质细胞活化；激活的小胶质细胞可能没有参与胶质瘤细胞的急性凋亡过程。%Objective: To study the changes in apoptosis of glioma cells and microglia activity and their correlation following nanosilver plus radiation.Methods:C6 glioma cells were stereotactically transplanted into the rat'right caudate nucleus.8 days after inoculation, the tumor-bearing animals were randomly divided into the irradiated control group and combined treatment group, which then received intratumoral injections of deionized water or nanosilver of the same volume ( 20 μg ) , followed by a single dose of ionizing radiation.The dynamic changes of apoptosis and microglia activity in the tumor tissue were examined by TUNEL assay and OX42 immunohistochemical staining, respectively.Results:The number of TUNEL-positive cells increased significantly 6 h after irradiation, and then dropped significantly 24 h postirradiation.Microglia activity was expressed 6 h after the radiation, and it grew further over time.Furthermore, compared with that in the irradiated control group, the number of TUNEL-positive cells and microglia activity increased significantly in the combined treatment group 6 h and 24 h after the radiation(P<0.001).The expression trends of microglia activity and TUNEL-positive cells were different, with the former being later.Conclusion:The combination of nanosilver with radiation can promote glioma cells apoptosis and activate microglia.The activated microglia may not participate in the acute process of glioma cell apoptosis.