燃煤砷暴露对人体T细胞增殖能力的影响及其机制探讨  

Influence of coal-arsenic exposure on human T cells proliferation and its mechanism

作　　者：谷俊莹[1] 张爱华[1] 张碧霞[2] 黄晓欣[2] 

机构地区：[1]贵阳医学院毒理学教研室,550004 [2]中国人民解放军第44医院

出　　处：《中国地方病学杂志》2009年第1期20-23,共4页Chinese Jouranl of Endemiology

基　　金：基金项目：教育部博士点基金（G2007-05）;贵州省科技厅课题（黔科合重大专项字[200616016）;贵州省“十一五”攻关项目（黔科合NY字[2006]3057）

摘　　要：目的探讨燃煤砷暴露对人体T细胞增殖能力的影响及其作用机制。方法采集贵州省燃煤污染型砷中毒病区居民及非病区居民外周血，按《地方性砷中毒诊断标准》（WS／T211-2001）分为暴露组（17例）、轻度砷中毒组（35例）、中度砷中毒组（38例）、重度砷中毒组（19例）及对照组（35例）。采用四甲基偶氮唑盐（MTT）比色法检测T细胞刺激指数；钙离子荧光探针（Fluo-3／AM）染色流式细胞术检测外周血单个核细胞（PBMC）钙离子指数（IECa2＋）；电泳迁移率改变实验（EMSA）检测PBMC活化T细胞核转录因子（NF—AT）结合DNA的活性。结果经刀豆蛋白A（ConA）刺激后，暴露组及轻、中、重度砷中毒组刺激指数（1．315±0．962、1．611±1．224、1．114±0．545、1．289±O．875）均低于对照组（2．322±1．241，P〈0．01）。经抗CD3单克隆抗体（McAb）刺激后．暴露组及轻、中、重度砷中毒组刺激指数（0．997±0．177、1．103±0．291、1．007±0．221、0．957±0．205）亦均低于对照组（1．842±0．429，P〈0．01）。轻、中、重度砷中毒组PBMC经抗CD3McAb处理后，IECa2＋（110．130±49．637、92．429±31．191、77．640±35．372）均显著低于对照组（145．986±59．450，P〈0．01）；中、重度砷中毒组IECa2＋亦均显著低于暴露组（121．337±46．410，P〈0．05）。轻、中、重度砷中毒组PBMC内NF—AT结合DNA活性（1．354±0．446、1．290±0．291、1．159±0．411）均显著低于对照组（1．722±0．291，P〈0．01）和暴露组（1．611±0．294，P〈0．05）。结论燃煤砷暴露可导致人体T细胞刺激指数下降、PBMC内IECa2＋减少及NF—AT结合DNA的活性降低．表明砷可抑制人体T细胞增殖能力，其原因可能与砷对T细胞受体（TCR）／CD3信号转导途径的影响有关。Objective To explore the influence of coal-arsenic exposure on human T cells proliferation and its mechanism. Methods Blood samples collected from individuals which lived in arsenism area of coal-burning type and non-arsenism area in Guizhou Province were divided into exposed group （17）, mild （35）, moderate（38） and severe arsenism group （19） and control group （35） according to Diagnosis Standard for Endemic Arsenism （WS/T 211-2001 ）. T cell stimulation index was determined by methyl thiazolyl tetrazolium （MTF） colorimetric method. The intracellular Ca2＋ exponential（IECa2_） in peripheral blood mononuclear cell（PBMC） was analyzed by Fluo-3/AM dye and flow cytometry. DNA binding activity of actively T cells nuclear factor（NF-AT） in PBMC was evaluated by electrophoretic mobility shift assay （EMSA）. Results Concanavalin A （ConA） stimulation decreased the T ceils stimulation indexes in exposed group, mild, moderate and severe arsenism groups（ 1.3i5 ±0.962, 1.611 ±1.224,1.114 ± 0.545,1.289 ± 0.875 ） compared with control group （2.322 ±1.241 ）, all the differences being statistically significant（P 〈 0.01）. After stimulated by anti-CD3 monoclonal antibody（McAb）, the T cells stimulation index in exposed group, mild, moderate and severe arsenism group（0.997 ±0.177,1.103 ± 0.291,1.007 ± 0.221, 0.957 ± 0.205） were lower than that of control group（ 1.842 ± 0.429, P 〈0.01 ）. IECa2＋ 0f PBMC after treated by anti-CD3 McAb in mild, moderate and severe arsenism group（ 110.130± 49.637,92.429 ± 31.191,77.640 ± 35.372） were lower compared with control group（145.986 ± 59.450, P 〈 0.01 ）. Moreover, IECa2＋ in moderat and severe arsenism group were lower than exposed group （121.337 ± 46.410, P 〈 0.05 ）. DNA binding activity of PBMC NF-AT in mild, moderate and severe arsenism group（ 1.354 ± 0.446,1.290 ± 0.291,1.159 ± 0.411 ） were lowered than that of control group （1.722± 0.291, P 〈 0.01 ） and exposed group （1.6

关 键 词：砷 煤 T淋巴细胞 细胞内游离钙 NFATC转录因子类 

分 类 号：R686[医药卫生—骨科学]