三氯乙烯药疹样皮炎细胞免疫学指标及发病机制研究硕士毕业论文.doc

目目 录录 中文摘要中文摘要1 英文摘要英文摘要6 英文缩写词表英文缩写词表12 前前 言言14 第一部分第一部分 tce 药疹样皮炎细胞免疫学指标及发病机制研究药疹样皮炎细胞免疫学指标及发病机制研究.19 第一节 tce 药疹样皮炎患者外周血淋巴细胞抗原特异性增殖功能测 定21 第二节 tce 药疹样皮炎患者外周血免疫细胞检测分析 .26 第三节 fas/fasl 与 pf/grb 介导的 tce 免疫毒作用机制探讨 37 小 结55 第二部分第二部分 8 例例 tce 药疹样皮炎患者病例报告分析药疹样皮炎患者病例报告分析.56 小 结71 总总 结结72 致致 谢谢74 参考文献参考文献76 附录附录 1 生物标志物的验证及其在健康危险预警中的作用生物标志物的验证及其在健康危险预警中的作用.86 附录附录 2 个人简历个人简历.96 1 三氯乙烯药疹样皮炎细胞免疫学指标及发病机制研究三氯乙烯药疹样皮炎细胞免疫学指标及发病机制研究 中文摘要中文摘要 职业接触三氯乙烯（trichloroethylene，tce）引起的 tce 药疹样皮炎是近 年来我国职业卫生领域令人关注的问题，但目前关于该病的发病机制尚不清楚， 对 tce 职业接触工人缺乏特异性健康监护指标，对 tce 药疹样皮炎患者缺乏 特异性临床治疗措施。 根据该病的发病特点一般认为其属于型超敏反应的可能性最大，型超 敏反应发生的机制与抗体和补体无关，主要是 t 细胞介导的免疫损伤。t 细胞 介导的免疫反应发生的过程涉及到记忆性 t 淋巴细胞的生成和效应性 t 细胞的 活化增殖，效应性 t 细胞通过分泌一系列细胞因子发挥作用，并调节 b 细胞、 nk 细胞以及其他各群免疫细胞的活化增殖。另外，细胞毒性 t 细胞（ctl） 在 t 细胞介导的超敏反应中发挥重要的作用，其主要通过两条途径杀伤靶细胞， 其一是穿孔素-颗粒酶途径，其主要参与免疫防御；其二是 fas-fasl 途径， fas/fasl 主要介导活化的效应性细胞凋亡，清除激活的外周 ctl，下调免疫应 答。这两条途径对于机体对外来抗原进行适度的免疫应答，维持免疫自稳发挥 重要作用。正常状态下，特异性淋巴细胞在外周免疫器官接受抗原刺激而大量 增殖，在免疫应答末期，机体通过 fas/fasl 细胞凋亡机制使发生活化的 t 细胞 凋亡，从而对免疫过程进行严密调控，以维持免疫自稳。因此，tce 药疹样皮 炎的的发生可能是由于机体免疫自稳状态被打破，发生过强的免疫应答反应所 致。 为验证上述假说，本研究采用成组设计的多个样本比较分析以及 tce 药疹 样皮炎患者入院治疗以及肝功能恢复正常时机体细胞免疫学指标的比较分析， 进一步探讨机体细胞免疫学指标的变化与 tce 药疹样皮炎的关系。研究结果如 下： 一、一、tce 药疹样皮炎细胞免疫学指标及发病机制研究药疹样皮炎细胞免疫学指标及发病机制研究 本研究选择三组研究对象，病例组为 16 例 tce 药疹样皮炎患者。接触对 2 照组为 32 例来自与病例同车间的从事 tce 作业的健康职业工人；非接触对照 组为 28 例从未接触过 tce 及其他职业性有害因素的的健康就业前体检工人。 三组研究对象按年龄性别进行匹配后，结果如下： 1.淋巴细胞抗原特异性增殖功能淋巴细胞抗原特异性增殖功能 16 例病人除皮疹外，还伴有不同程度的肝损害，谷丙转氨酶（alt）水平 升高者 15 例（93.33%）；谷草转氨酶（ast）升高者 12 例（73.33%）。三组 研究对象外周血淋巴细胞分别与不同浓度 tce（0.2mmol/l、1 mmol/l、5 mmol/l）共培养，在各组内随着 tce 染毒浓度的增加外周血淋巴细胞的存活 率逐渐降低，差异有统计学意义(p0.05)，提示 tce 本身具有细胞毒性，而在 tce 药疹样 皮炎患者以及 tce 接触对照体内并不存在针对 tce 原形的特异性记忆性淋巴 细胞。 2.外周血淋巴细胞亚群分析外周血淋巴细胞亚群分析 研究对象血常规检测结果发现，16 例病人中有 6 例（37.5%）病人外周血 淋巴细胞（lymp）高于临床正常参考值范围，1（6.25%）例低于临床正常参 考值范围；6 例（37.5%）单核细胞（mono）高于临床正常参考值范围；14 例（87.5%）中性粒细胞（neut）高于临床正常参考值范围；8 例（50%）嗜 酸性粒细胞（eo）高于临床正常参考值范围，2 例（12.5%）低于临床正常参 考值范围，8 例（50%）嗜碱性粒细胞（baso）高于临床正常参考值范围。在 接触对照组和非接触对照组体内上述指标均在临床正常参考值范围内。提示 tce 药疹样皮炎患者体内免疫细胞的数量发生异常，由于外周血免疫细胞的改 变与组织内免疫细胞的浸润密切相关，尤其是嗜酸性粒细胞主要分布于人体内 呼吸道、消化道和泌尿生殖道粘膜组织中，其水平的升高可能与 tce 药疹样皮 炎病人出现的眼、口、生殖器等处的粘膜损伤有关。 结合血常规与流式细胞术检测的结果，比较各组之间淋巴细胞亚群在外周 血中的变化情况。结果发现病例组外周血淋巴细胞总数、t 细胞、cd4+t 细胞 计数均明显高于接触对照组和非接触对照组(p0.05)，提示这三个指标可作为 tce 药疹样皮炎的疾 病标志； cd8+t 细胞和 cd8+cd28-t 细胞三组之间比较为病例组接触对照组非 3 接触对照组，各组间差异有统计学意义(p0.05） ；病例组与接触对照组外周血 cd4+t 细胞表面 fasl 阳性表达的百分比均高于非接触对照组（p0.05） ；cd8+t 细胞表面 fasl 阳性表达的百分比呈现 病例组接触对照组非接触对照组，组间差异有统计学意义（p0.05)。grb 在病例组的表达高于非接 触对照组 (p0.05)。提 示在病例组工人体内活化的 ctl 通过 fas/fasl 途径清除了一部分，但由于同时 表达 fasl 的 cd8+ctl 随血液循环迁移至皮肤、肝脏、肾脏等组织器官，通过 与这些组织细胞表面的 fas 蛋白结合介导靶细胞的凋亡。同时病例组体内通过 活化的 ctl 高表达 pf 和 grb 蛋白，介导皮肤角质细胞的死亡，引起 tce 药 疹样皮炎患者皮肤的损伤。而健康的 tce 接触对照工人体内也存在活化的细胞 毒性 t 细胞（cd4+ctl 与 cd8+ctl） ，但并没有发病，其原因仍有待进一步研 究。 病例组外周血 fas mrna 表达高于接触对照组（1.2622 倍）与非接触对照 组（1.1383 倍）,接触对照组低于非接触对照组（0.9019 倍）；病例组外周血 fasl mrna 表达高于接触对照组（1.4239 倍）与非接触对照组（1.7507 倍）， 接触对照组低于非接触对照组（0.8133 倍）。病例组（0.8166 倍）与接触对照 组（0.6009 倍）pf mrna 表达低于非接触对照组，而病例组高于接触对照组 （1.3590 倍）。病例组 grb mrna 表达低于接触对照组（0.4477 倍）与非接触 对照组（0.4835 倍），接触对照组高于非接触对照组（1.0800 倍）。此研究结 果与 fas、fasl、pf、grb 蛋白的表达情况不完全一致，是由于 mrna 的表 达在转录和翻译水平均受到多种因素的调节。 4 二、二、8 例例 tce 药疹样皮炎病例报告分析药疹样皮炎病例报告分析 对 8 例 tce 药疹样皮炎的病人入院治疗时及肝功能恢复正常时（转归时） 各指标进行比较分析，进一步探索 tce 药疹样皮炎病人体内各免疫学指标的变 化以及可用于评价临床治疗效果的指标，并结合前面病例与对照实验研究结果 对 tce 药疹样皮炎与各细胞免疫学指标的关系进行综合分析。 1.各群淋巴细胞检测分析各群淋巴细胞检测分析 获得 6 例病人入院治疗时及转归时淋巴细胞检测结果资料。与临床正常参 考值相比较，6 例（100%）病人入院时 neut 均升高，1 例病人肝功能恢复正 常时 neut 仍高于正常参考值范围；入院时 eo 升高者有 4 例（66.67%）； baso 和 lymph 升高者分别有 3 例（50%）；mono 升高者有 2 例(33.33%)， 出院时仍有 1 例病人 mono 升高。 对 6 例病人入院和转归时血常规结果进行比较，其中 6 例（100%）病人入 院时 neut 与 baso 均升高，5 例（83.33%）病人 lymph、mono、eo 均升 高。提示 tce 药疹样皮炎患者在发病的初期机体正在进行着免疫反应，与第一 部分研究结果相一致。 对 6 例病人入院和转归时淋巴细胞亚群分析结果进行比较，6 例病人中有 4 例（66.67%）在入院时 t 淋巴细胞升高，b 淋巴细胞有 3 例（50%）升高，4 例（66.67%）nk 细胞降低。入院时 4 例（66.67%）cd4+t 淋巴细胞明显增多， 4 例（66.67%）cd8+t 淋巴细胞明显增多。cd8+cd28+t 有 3 例（50%）入院 时降低，cd8+cd28-t 有 5 例（83.33%）入院时升高。6 例病人中有 4 例在入院 时 cd4+/cd8+比值降低，4 例 cd28+/cd28-细胞的比值降低。提示 tce 药疹样 皮炎患者在发病初期机体内各群免疫细胞的数量与比例发生变化。 2.外周血外周血 fas/fasl、pf/grb 的测定的测定 与疾病转归时相比较，入院时 6 例病人中有 4 例（66.67%）fas 表达阳性 cd4+t 细胞百分比升高；3 例(50%)病人 fas 阳性 cd8+t 细胞百分比升高。6 例病人中有 3 例(50%) fasl 阳性 cd4+t 细胞升高；3 例(50%)病人 fasl 阳性 cd8+t 细胞升高。而两例入院检测前未经激素治疗的病例外周血入院时 fas 表 达阳性 cd4+t 细胞百分比降低、fas 阳性 cd8+t 细胞百分比升高、fasl 阳性 cd8+t 细胞升高，提示病例在发病的早期 cd4+ctl 未发挥负调节免疫应答的 5 作用，未及时清除活化的 t 细胞。cd8+ctl 通过 fas/fasl 途径介导了 tce 药 疹样皮炎患者的病例损伤。3 例(100%)病人在外周血中 pf 表达阳性淋巴细胞百 分率均高于出院时。1 例(33.33%)病人外周血中 grb 表达阳性细胞百分率高于 出院时。提示在 tce 药疹样皮炎的发病早期，pf 通过杀伤皮肤角质细胞介导 tce 药疹样皮炎患者的皮肤损害。此与第一部分研究结果相一致。 总之，本研究通过病例与对照实验研究以及病例入院和转归时细胞免疫学 指标的比较分析，揭示 tce 药疹样皮炎的发生可能是由其代谢产物而非 tce 本身引起，tce 药疹样皮炎的发生与体内免疫细胞的活化增殖有关，tce 暴露 能诱导人外周血淋巴细胞亚群的数量发生变化，其中总淋巴细胞、t 细胞和 cd4+t 细胞计数升高可能作为 tce 接触工人发生药疹样皮炎的的临床筛检指标， cd3-cd56+细胞计数降低、cd8+t 细胞计数升高以及 cd8+cd28-t 计数升高可 作为反映 tce 接触的效应指标。cd4+ctl 细胞通过表达 fas 介导活化的 t 细 胞凋亡，维持机体的免疫自稳。cd8+ctl 通过表达 fasl 并随血液循环与皮肤、 肝脏、肾脏等组织细胞表面 fas 结合介导靶细胞凋亡，引起组织器官的免疫性 损伤。ctl 通过 pf/grb 途径介导 tce 药疹样皮炎患者的皮肤损害。因此本研 究为 tce 接触工人的健康监护具有重要指导意义和参考价值，并对 tce 药疹 样皮炎病人采取针对性的免疫治疗措施提供理论依据。 关键词：关键词：三氯乙烯，细胞免疫，药疹，接触性过敏性皮炎，半抗原，细胞毒性 t 细胞，淋巴细胞亚群，职业接触 6 study on index of cell-mediated immunity and pathogenesis of dermatitis medicamentosa-like of trichloroethylene 英文摘要英文摘要 abstract dermatitis medicamentosa-like of trichloroethylene(dmlt) in workers appears to be an occupational health issue and has aroused general concern in china in recent years. however, little is known about its pathogenesis to date, there are also lack of specific indexes for health surveillance as well as specific measures for clinical treatment. dmlt may involve in type hypersensitivity according to its characteristics. formation of t memory lymphocytes and proliferation are the two steps of cell- mediated immunity. activated t cells regulate the proliferation of nk and b cells through secrete a series of cytokines. cytotoxic t lymphocytes(ctl) play an important part in cell-mediated immune system. its cytotoxicity can be induced by two ways: a) granuledependent exocytosis pathway, which participate immune defenses. b) fas-fasl intercellular linkage-mediated pathway, which down-regulate immune response through clean activated peripheral ctl at the end of the immune response. the two ways play an important role in maintaining the immune homeostasis. the process of dmlt may related to the proliferation of lymphocytes and the function of ctl. those two approaches play an important role in cleaning 7 foreign antigens to maintain immune homeostasis. in normal condition, specific immune lymphocytes which stimulated by antigen proliferate in peripheral immune organs. in the end of the immune response, the activated cells apoptosis through fas/fasl pathway, thus to control the immune process and maintain immune homeostasis. therefore, dmlt might be induced by activated cells which were not cleared in time, and strong immune response breakout. in order to test the above hypothesis, we conducted a three groups design analysis and cases analysis to explore the relationship between abnormal index of cell-mediated immunity and dmlt. the results were as follows: 1. study on index of cell-mediated immunity and pathogenesis of dmlt there are there groups in this study: case group, cases are 16 patients of dmlt, all examinations executed on admission; tce-exposure group, 30 workers came form the workshops the cases occurred but no skin disorders examined by the occupational physicians after the first 3 months of tce exposure. healthy worker group, 28 workers were never exposed to tce and no history of previous skin disease. the main results are as follows: .test for functions of antigen-specific lymphocyte proliferation 16 patients with severe rash, accompanied by different degree of liver damage, 15 cases (93.33%) in 16 with higher alt and 12 cases (73.33%)in 16 with higher ast. peripheral blood lymphocytes(2106/ml) of three groups cultured with different concentrations tce (0.2mmol/l,1mmol/l, 5mmol/l). in any group, peripheral blood lymphocyte survival rates gradually reduced with the increase of tce concentration. no significant difference was found about survival rates of lymphocytes under the same concentrations in three groups. the result suggest that tce performed great cell toxicity on peripheral blood lymphocytes, and there was no tce-specific memory lymphocyte. . analysis of lymphocyte subsets in peripheral blood from the routine blood test of 16 patients, 6 cases(37.5%) peripheral blood lymphocyte(lymp) higher than the normal clinical range, 1(6.25%) below the 8 normal clinical range; 6 cases(37.5%) mononuclear cells (mono) higher than normal reference range of clinical; 14 cases(87.6%) neutrophils neut) higher than normal clinical range; 8 cases(50%) eosinophils(eo) higher than normal clinical range, 2 cases (12.5%) below the normal clinical range; 8 cases (50%) basophilic granulocyte (baso) higher than the normal range of clinical range. in both healthy tce-exposed workers and unexposed workers, the indexes are all in clinical normal reference ranges. those indicate immune response on going in patients of dmlt. the change of peripheral immune cells are closely related to the organization of immune cell infiltrates, human eosinophils mainly distributed in the respiratory tract, enteron and genitourinary tract mucosa tissue, the increase of eo in peripheral blood might relate to the damage of mucous membrane in eye, mouth and genital of patients. the absolute counts of lymphocyte, t cell, cd4+ t cell were significantly increased in patients with hypersensitivity dermatitis compared with healthy tce- exposed workers and unexposed workers(p0.05), so those three indexes could be disease markers of dmlt. cd8+ t cell, cd8+cd28- t cell counts among the three groups showed case groupexposed groupunexposed control group, and the difference was significant(p0.05). the percentage of cd4+cd178+t cell in cd4+t cell in case and exposed group are higher than unexposed group(p0.05), no significant difference between case group and unexposed group(p0.05).the 9 percentage of cd8+cd178+t cell in cd8+t cell among the three groups showed case groupexposed groupunexposed control group, and the difference was significant (p0.05). it indicate ctl (cd4+ctl and cd8+ctl) induce apoptosis of effector cells in healthy tce-exposed workers. however, in cases, some ctls are removed through fas/fasl pathway, others migrate to skin, liver, kidney, etc, and mediated the target cell apoptosis. meanwhile, the high expression of pf and grb cause skin damage in cases. in case group the expression of fas mrna is higher than exposed(1.2622 fold) and unexposed group(1.1383 fold), exposed group is lower than unexposed group(0.9019 fold); in case group the expression of fasl mrna is higher than exposed(1.4239 fold) and unexposed group(1.7507 fold), exposed group is lower than unexposed group(0.8133 fold); in case (0.8133 fold)and exposed group (0.6009 fold)the expression of pf mrna are lower than unexposed group, in case group (1.3590 fold)is higher than unexposed group. in case group the expression of grb mrna is lower than exposed(0.4477 fold) and unexposed group(0.4835 fold), exposed group(1.0800 fold) is higher than unexposed group. the expression of fas, fasl, pf, grb in protein and mrna level are not identical, that is due to the expression of mrna in transcription and translation are regulated by various factors. 2. 8 cases report of dmlt compare the differences of dmlt when hospitalized and liver function recovered to normal, further explore the indexes of immunological changes and that could be used to evaluate the clinical treatment effect, and combining with the former group analysis to analyze the relationship between immunological indexes and dmlt. .analysis of lymphocyte subsets there are lymphocyte results of six patients when hospitalized and liver function recovered to normal. neut in 6 cases(100%) were higher when checked into hospital; 10 4 in 6 cases(66.67%)had a higher eo than normal clinical range; 3 in 6(50%) cases had a higher baso and lymph than normal clinical range. 6 cases(100%) had higher neut and baso, 5 cases in 6 had higher lymph、mono and eo when hospitalized than liver function recovered to normal. those indicate immune function disorder in dmtl, all consistent with the former results. lymphocyte subsets analysis results of six patients in hospital and liver back to normal, 4 cases (66.67%)in 6 have significantly higher t lymphocytes in admission; b lymphocytes, 3 cases (50%) was obviously higher than normal liver, 4 cases (66.67%) nk cell below normal liver. on admission, 4 cases (66.67%) cd4+t lymphocyte increased obviously, 4 cases (66.67%) cd8+t lymphocytes increased obviously. in 3(50%)cases cd8+cd28+t below in admission, 5 cases (83.33%) cd8+cd28-t higher than liver back to normal. 4 patients in 6 patients (66.67%) cd4+/cd8+ ratio decreased when hospitalized, 4 cases cd28+/cd28- cell ratio decreased. it indicated there are changes of immune cells number and proportion onset of dmlt. case 1, 5, and 6 discharged from hospital when the liver function returning to normal. nk cells elevated、 cd28+cd8-t cells reduced and the ratio of cd4+/cd8+ returned to normal in 3 patients when discharged from hospital. those three indexes could be the index of rehabilitation. in case 1 and case 6, t lymphocytes、cd8+t lymphocytes declined when discharged from hospital, it might be a reference index of rehabilitation. .examination of fas/fasl、pf/grb expression of protein and mrna in peripheral blood 4 patients in 6 (50%) the percentage of fas+cd4+t cells in cd4+t were higher when hospitalized 、3 patients (50%) patients the percentage of fas+cd8+tcells in cd8+t were higher at admission than normal liver function, 3 patients in 6 (50%) the percentage of fasl+cd4+t cells in cd4+t were lower, 3 cases (50%) the percentage of fasl+cd8+t cells in cd8+t were lower than rehabilitation. those results are consistent with the former results. 11 pf protein in peripheral lymphocyte was higher in 3 cases(100%) when hospitalized than liver function recovered to normal; 1 in 3 cases(33.33%) grb protein in peripheral lymphocyte was higher when hospitalized than liver function recovered to normal. it indicated pf damage skin keratinized cell at the early stage of dmlt. in summary, this study revealed the immune response in dmlt might induced by the metabolites of tce rather than tce itself. there were great changes in dmlt about lymphocyte subsets in peripheral blood. lymphocyte, t cell, cd4+t cell could be disease markers of dmlt, cd8+t, cd8+cd28- t and nk cell could be effect makers for tce exposure. ctls take part in the damage of skin 、liver、kidney and some other organs. those results could make some significance to health surveillance of tce exposure and provide possibility for further studies in pathogenesis. key words: trichloroethylene，cell-mediated immunity，drug rash，allergic contact dermatitis，hapten，cytotoxic t lymphocyte，lymphocyte subsets, occupational exposure 12 英文缩写词表英文缩写词表 （list of abbreviation） acdallergic aminotransferase过敏性接触性皮炎过敏性接触性皮炎 adatopic dermatitis特应性皮炎特应性皮炎 adhalcohol dehydrogenase醇脱氢酶醇脱氢酶 altglutamic-pyruvic transaminase谷丙转氨酶谷丙转氨酶 aldhaldehydedehydrogenase醛脱氢酶醛脱氢酶 astglutamic-oxaloacetic transaminase谷草转氨酶谷草转氨酶 basobasophils嗜碱性粒细胞嗜碱性粒细胞 cdcluster of differentiation分化抗原分化抗原 chscontact hypersensitivity接触性超敏反应接触性超敏反应 ctlcytotoxic t lymphocyte细胞毒性细胞毒性 t 细胞细胞 cyp450cytochtome p450细胞色素细胞色素 p450 酶系酶系 dcvg(1,2-dichlorovinyl)glutathione1,2-二氯乙烯基谷胱甘肽二氯乙烯基谷胱甘肽 dcvc(1,2-dichlorovinyl)-l-cysteine1,2-二氯乙烯基半胱氨酸二氯乙烯基半胱氨酸 dmlt dermatitis medicamentosa-like of trichloroethylene 三氯乙烯药疹样皮炎三氯乙烯药疹样皮炎 dmsodimethylsulfoxide二甲基亚砜二甲基亚砜 edtadisodium thylenediaminetetra acetate乙二胺四乙酸乙二胺四乙酸 eoeosnophils嗜酸性粒细胞嗜酸性粒细胞 faslfas ligand外周血淋巴细胞外周血淋巴细胞 13 fcsfetal calf serum胎牛血清胎牛血清 ggtglutamine transferase谷氨酰胺转移酶谷氨酰胺转移酶 grbgranzyme b颗粒酶颗粒酶 b gshglutathione谷胱甘肽谷胱甘肽 gstsglutathione s-tranferase谷胱甘肽转移酶谷胱甘肽转移酶 iarc international agency for research on cancer 国际癌症研究署国际癌症研究署 ilinterleukin白细胞介素白细胞介素 ifninterferon干扰素干扰素 lymplymphocyte count淋巴细胞计数淋巴细胞计数 mfimean fluorescent intensity平均荧光强度平均荧光强度 monomonocytes单核细胞单核细胞 mttmethyl thiazolyl tetrazolium噻唑兰噻唑兰 natsn-acetyltranferasen-乙酰转移酶乙酰转移酶 neutneutrophils中性粒细胞中性粒细胞 nirsnonimmediate allergic reactions非速发型超敏反应非速发型超敏反应 nk cellnatural killer cell自然杀伤细胞自然杀伤细胞 pbsphosphate buffered saline磷酸盐缓冲液磷酸盐缓冲液 pfperforin穿孔素穿孔素 semstandard error of mean标准误标准误 sjsstevens-johnson syndrome斯蒂文斯约翰综合症斯蒂文斯约翰综合症 tcatrichloroacetic acid三氯乙酸三氯乙酸 tcetrichloroethylene三氯乙烯三氯乙烯 tnetoxic epidermal necrolysis中毒性表皮坏死松解症中毒性表皮坏死松解症 tnftumor necrosis factor肿瘤坏死因子肿瘤坏死因子 udpgtudp-glucuronyl transferase 尿苷二磷酸尿苷二磷酸-葡萄糖醛酸转葡萄糖醛酸转 移酶移酶 14 前前 言言 三氯乙烯背景资料：三氯乙烯背景资料： 1.理化性质 三氯乙烯（trichloroethylene, tce）是由碳、氢、氧三种元素组成的无色、 透明、不燃烧、易挥发具有芳香味的液体。分子式：c2-h-cl3。分子量 131.39。相对密度 1.4649g/cm3(20/4)。熔点-73。沸点 86.7。闪点 32.22 (闭杯)。自燃点 420。蒸气密度 4.53。蒸气压 13.33kpa(100mmhg32)。蒸气 与空气形成混合物可燃限 8.0%10.5%。几乎不溶于水；与乙醇、乙醚及氯仿 混溶；溶于多种固定油和挥发性油。潮湿时遇光生成盐酸。高浓度蒸气在高温 下会燃烧。加热分解，放出有毒氯化物。加热至 250-600，与铁、铜、锌、铝 接触生成光气。能与钡、四氧化二氮、锂、镁、液态氧、臭氧、氢氧化钾、硝 酸钾、钠、氢氧化钠、钛发生剧烈反应。 2.主要用途 自 19 世纪初期，tce 的在工业上应用广泛，可用作金属脱脂和羊毛及织 物的干洗剂1。树脂、沥青、煤焦油、醋酸纤维素、硝化纤维素、橡胶和涂料 等的溶剂。在医药上用作麻醉剂，农药上是合成一氯醋酸的原料。由于其挥发 性和溶解能力极强，并且通常条件下不燃，沸点适中，蒸汽压力高，稳定性强， 适合于气洗操作，在工业上广泛用于金属清洗（脱脂彻底）和纤维脱除油脂1。 利用其溶解力强的特性，常用于清除难于清除的污垢，如半硬化的清漆、涂层 剖光剂、较厚的助焊剂。也用于萃取剂、溶剂和低温导热油介质。作为原料中 间体可用于生产四氯乙烯、氯乙酸、二氯乙酰氯、八氯二丙醚，hcfc- 15 123、hcfc-124、hfc-125、hfc-134a 等。但其主要的应用领域是作为清 洗剂使用，目前我国已经成为全球电子电气产品主要生产国，2004 年清洗剂领 域消耗 tce 约 4.9 万吨。据海关统计，2004 年广东地区进口 1 万余吨的三氯乙 烯的 90%是用于电子原件的清洗2。 3.健康危害 tce 有刺激和麻醉作用，吸入急性中毒者有上呼吸道刺激症状、流泪、流 涎。随之出现头晕、头痛、恶心、运动失调及酒醉样症状。当出现头晕、头痛、 倦睡、恶心、呕吐、腹痛、视力模糊、四肢麻木，甚至出现兴奋不安、抽搐乃 至昏迷，可致死。慢性影响：有乏力、眩晕、恶心、酩酊感等。可有肝损害。 皮肤反复接触，可致皮炎和湿疹。对中枢神经系统有抑制作用亦可累及周围神 经系统和心、肝、肾等实质脏器。能提高交感神经的反应性，并使其递质生成 增加，从而使心脏对刺激的敏感性增高。职业性 tce 中毒，是工作中接触高浓 度 tce 蒸汽或液体所引起的以神经系统改变为主的全身性疾病，除神经系统外， 心、肝、肾亦可累及。近年来，我国关于 tce 的健康危害，主要集中在职业人 群中的 tce 引起的药疹样皮炎，该病以全身的皮肤损害为主要表现，同时伴有 发热、浅表淋巴结肿大、皮肤红肿糜烂等症状，病情严重者可因心、肝、肾功 能衰竭和/或合并细菌感染而死亡。 4.代谢 tce的吸收和排出随其脂溶度、水溶度、空气中浓度和机体通气量等因素 而定。可经呼吸道、消化道和皮肤吸收。吸收后主要蓄积于肝脏、脑和心脏等 器官3。其中10%20未经代谢的tce可以原形自呼吸道中排出，也可以在体 内代谢后经尿排出，随尿排出的两种主要代谢物三