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-东南大学学报医学版

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

单位：1. 东南大学医学院神经生物学研究所, 江苏南京 210009;
2. 东南大学江苏省生物材料与器件重点实验室, 江苏南京 210009

分类号：R739.41;R329.25

出版年·卷·期（页码）：2015·34·第五期（679-683）

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20 μg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.

参考文献：

[1] HUANG R Y,NEAGU M R,REARDON D A,et al.Pitfalls in the neuroimaging of glioblastoma in the era of antiangiogenic and immuno/targeted therapy-detecting illusive disease,defining response[J].Front Neurol,2015,6:33.
[2] BRETT-MORRIS A,WRIGHT B M,SEO Y,et al.The polyamine catabolic enzyme SAT1 modulates tumorigenesis and radiation response in GBM[J]. Cancer Res,2014,74(23):6925-6934.
[3] XU R,MA J,SUN X,et al.Ag nanoparticles sensitize IR-induced killing of cancer cells[J].Cell Res,2009,19(8):1031-1034.
[4] LIU P,HUANG Z,CHEN Z,et al.Silver nanoparticles:a novel radiation sensitizer for glioma?[J].Nanoscale,2013,5(23):11829-11836.
[5] CUI Y,MENG H,LIU W,et al.Huaier aqueous extract induces apoptosis of human fibrosarcoma HT1080 cells through the mitochondrial pathway[J].Oncol Lett,2015,9(4):1590-1596.
[6] GUTMANN D H.Microglia in the tumor microenvironment:taking their TOLL on glioma biology[J].Neuro Oncol,2015,17(2):171-173.
[7] SARKAR S,DRING A,ZEMP F J,et al.Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells[J].Nat Neurosci,2014,17(1):46-55.
[8] SHAO W,GU J,HUANG C,et al.Malignancy-associated metabolic profiling of human glioma cell lines using 1H NMR spectroscopy[J]. Mol Cancer,2014,13:197.
[9] MIYAKE J A,BENADIBA M,RIBEIRO G,et al.Novel ruthenium-gamma-linolenic acid complex inhibits C6 rat glioma cell proliferation in vitro and in the orthotopic C6 model in vivo after osmotic pump infusion[J].Anticancer Res,2014,34(4):1901-1911.
[10] AN Y,GUO W,LI L,et al.Micheliolide derivative DMAMCL inhibits glioma cell growth in vitro and in vivo[J].PLoS One,2015,10(2):e0116202.
[11] GARCIA-BARROS M,PARIS F,CORDON-CARDO C,et al.Tumor response to radiotherapy regulated by endothelial cell apoptosis[J].Science,2003,300(5622):1155-1159.
[12] LU F,LI Y Q,AUBERT I,et al.Endothelial cells regulate p53-dependent apoptosis of neural progenitors after irradiation[J]. Cell Death Dis,2012,3:e324.
[13] 梁瑞,吴鹤,戚基萍.活化的小胶质细胞在脑出血后的作用[J].现代医学,2015,43(2):262-265.
[14] LOURBOPOULOS A,ERTVRK A,HELLAL F.Microglia in action:how aging and injury can change the brain's guardians[J].Front Cell Neurosci,2015,9:54.
[15] CHAO T H,CHANG M Y,SU S J,et al.Inducible nitric oxide synthase mediates MG132 lethality in leukemic cells through mitochondrial depolarization[J].Free Radic Biol Med,2014,74:175-187.
[16] 刘培党,史婷婷,朱建宝,等.纳米银联合放疗对大鼠胶质瘤内iNOS表达和NO水平的影响[J].神经解剖学杂志,2013,29(3):275-279.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录