三氯乙醇和三氯乙酸在诱发三氯乙烯药疹样皮炎中的作用  

Roles of trichloroethanol and trichloroacetic acid in trichloroethylene-induced hypersensitive dermatitis

作　　者：伊梦楠 臧丹[1,2] 易娟 刘帅 周伟[3] 王俊程 沈美丽 王婷[1] 段化伟[1] 黄先青[3] 戴宇飞 YI Mengnan;ZANG Dan;YI Juan;LIU Shuai;ZHOU Wei;WANG Juncheng;SHEN Meili;WANG Ting;DUAN Huawei;HUANG Xianqing;DAI Yufei(Key Laboratory of Chemical Contaminants and Health/Institute of Occupational Health and Poison Control,Chinese Center for Disease Control and Prevention,Beijing 100050,China;Beijing Fengtai District Market Supervision Administration,Beijing 100050,China;Shenzhen Preventive and Treatment Center for Occupational Diseases,Shenzhen,Guangdong 510000,China)

机构地区：[1]中国疾病预防控制中心,职业卫生与中毒控制所/化学污染物与健康重点实验室,北京100050 [2]北京市丰台区市场监督管理局,北京100050 [3]深圳市职业病防治院,广东深圳510000

出　　处：《环境与职业医学》2021年第10期1113-1118,共6页Journal of Environmental and Occupational Medicine

基　　金：国家自然科学基金项目(81773477);国家科技支撑计划(2014BAI12B02)。

摘　　要：[背景]三氯乙烯职业暴露是导致药疹样皮炎发病的主要原因,然而其代谢产物是否参与疾病的发生尚不明确。[目的]检测三氯乙烯的代谢产物三氯乙酸和三氯乙醇的致敏性,进一步探讨二者在诱发三氯乙烯药疹样皮炎(TIHD)中的作用。[方法]体外细胞研究通过培养人髓系白血病单核细胞株(THP-1),设置三氯乙酸和三氯乙醇染毒浓度为0、0.5、1.0、2.0、4.0 mmol·L^(-1),采用ELISA法检测上清中白细胞介素-8(IL-8)的表达水平;采用Western blotting法检测诱导型一氧化氮合酶(iNOS)的表达水平。人群研究分别设置三氯乙烯非接触对照组(20人)、三氯乙烯接触对照组(20人)、TIHD入院病例组(10人)和TIHD出院病例组(7人),共57人,利用淋巴细胞分离液分离其外周血单个核细胞后,加入0.5、2.0 mmol·L^(-1)的三氯乙酸和三氯乙醇进行染毒处理,利用CCK-8法检测外周血单个核细胞存活率。[结果]体外细胞研究结果:随着染毒剂量增高,三氯乙酸和三氯乙醇对THP-1细胞毒性逐渐增加,并且THP-1细胞IL-8表达水平逐渐增高,表现出剂量依赖性(相关分析,均P<0.05);与未染毒组相比,在1.0、2.0、4.0 mmol·L^(-1)染毒剂量下,三氯乙酸染毒组IL-8水平分别增加了116.30%、176.08%、541.18%,三氯乙醇染毒组IL-8水平分别增加了176.08%、366.70%、670.48%(P<0.05);Western blotting检测结果显示,与空白对照组相比,1.0、2.0、4.0 mmol·L^(-1)三氯乙酸组iNOS的表达水平分别增加了93.73%、87.08%、238.06%(P<0.05),1.0、2.0、4.0 mmol·L^(-1)三氯乙醇组iNOS的表达水平分别增加了95.99%、486.29%、735.72%(P<0.05)。人群研究结果显示:与非接触对照组相比,出院病例组外周血单个核细胞经0.5、2.0 mmol·L^(-1)三氯乙酸处理后细胞存活率分别增加了5.81%、5.64%(P<0.05);而在该组人群三氯乙醇处理后的细胞存活率变化未见统计学意义(P>0.05);同样,三氯乙烯接触对照组、入院病例组的外周血[Background]Occupational exposure to trichloroethylene(TCE)is a major cause of dermatitis;however,whether its metabolites are involved in the development of the disease is unclear.[Objective]This study aims to evaluate the sensitization of trichloroacetic acid and trichloroethanol and to investigate their roles in the TCE-induced hypersensitive dermatitis(TIHD).[Methods]Human myeloid leukemia mononuclear cells(THP-1)were cultured in vitro and exposed to trichloroacetic acid or trichloroethanol at 0,0.5,1.0,2.0,and 4.0 mmol·L^(-1),respectively.Interleukin-8(IL-8)was detected by ELISA;inducible nitric oxide synthase(iNOS)was detected by Western blotting.A total of 57 individuals participated in a population-based study,including a TCE non-exposure control group,a TCE exposure group,a TIHD admitted group,and a TIHD discharged group.Peripheral blood mononuclear cells were separated by lymphocyte isolation solution and exposed to 0.5 and 2.0 mmol·L^(-1) trichloroacetic acid or trichloroethanol.Their survival rates were estimated by CCK-8.[Results]The toxicity of trichloroacetic acid or trichloroethanol on THP-1 cells increased in a dose-dependent manner,and the IL-8 levels in THP-1 cells also increased gradually with the increase of exposure dose in a dose-dependent manner(P<0.05).Compared with the control group,the IL-8 levels increased by 116.30%,176.08%,and 541.18%in the 1.0,2.0,and 4.0 mmol·L^(-1) trichloroacetic acid groups and by 176.08%,366.70%,and 670.48%in the 1.0,2.0,and 4.0 mmol·L^(-1) trichloroethanol groups,respectively(P<0.05).The results of Western blotting indicated that compared with the control group,the iNOS levels in the 1.0,2.0,and 4.0 mmol·L^(-1) trichloroacetic acid groups increased by 93.73%,87.08%,and 238.06%(P<0.05),and the levels in the 1.0,2.0,and 4.0 mmol·L^(-1) trichloroethanol groups increased by 95.99%,486.29%,and 735.72%(P<0.05),respectively.In the population-based study,compared with the non-exposure control group,the survival rates of peripheral blood mononuclear cells exposed

关 键 词：三氯乙烯 三氯乙酸 三氯乙醇 致敏性 药疹样皮炎 

分 类 号：R135[医药卫生—劳动卫生]