【作者】 刘扬；

【导师】 徐兆发；

【作者基本信息】 中国医科大学 ， 劳动卫生与环境卫生学， 2002， 博士

【摘要】 前言 人类使用铅已有数千年历史。铅中毒也一直伴随着它的使用存在。由于铅的应用非常广泛，对它的研究仍是重金属毒理研究领域中最重要的内容之一。 随着科学技术的进步，铅的生产条件也在不断改进。发达国家由于没有高浓度铅作业环境，铅的流行病学研究多集中于低浓度铅的健康效应上。而在我国，特别是一些中小企业，劳动环境很差，工人仍处在高浓度铅的暴露中，其健康危害是不容忽视的。我们所调查的沈阳冶炼厂，生产铅的技术水平仅为发达国家70年代初的水平，工人作业环境空气中铅的浓度很高。我们选择的低浓度铅暴露人群来自冶炼厂烟波着地点范围内的沈阳低压开关厂，这里的工人们虽未参加铅的作业，却暴露在较高铅浓度的空气环境中。本研究是在此背景下进行的。 量效关系的研究多见于上世纪铅污染的早期。而现在对铅效应指标的分析手段更加准确和敏感，重新评估铅与卟啉代谢产物的量效关系，对于确定铅作业工人铅暴露的可接受上限值和诊断值、开展健康监护和健康诊断以及制定卫生标准有重要意义。 铅对血压的影响目前尚无定论。我国是一个高血压高发国家，控制高血压的流行是卫生工作的重点。铅能否成为高血压的危险因素之一需要澄清。 ALAD基因多态性研究是当前沿对卟啉代谢影响研究的热点。是人类遗传基因对职业或环境因素易感性研究的一个方面。它将对于就业人员的限定和保护高危险人群有重要的作用。 材料与方法 本研究选取沈阳冶炼厂铅生产工段工人150名和沈阳低压开关厂机械加工和电器维修工段工人70名作为调查对象。均为男性，平均年龄分别为36．00 t 7．37岁和33．54＊8．49岁。问卷调查项目主要以”沈阳市接触铅作业工人健康检查表”为基础，并增加了一些症状、既往病史、家族史、吸烟史、饮酒史、疗养史、驱铅治疗情况和工人在作业场所的卫生习惯等项目。作业现场空气铅浓度来自于调查前后两厂环保科的监测结果。取调查对象外周血SInl，分别测定其血铅人LA－D门一氨基乙酸雨酸脱水酶XALA－P（血浆8一氨基乙酸丙酸XALA－U（尿5一氨基乙酸雨酸＊Hi（血容积）和Hb（血红素厂并对受试者的血压进行了测定。在230名样本中选择出11名血铅浓度较低，ALA－D值下降幅度大的个体作为敏感人群进行ALA－D基因多态性分析。 血铅采用无火焰原子分光光度计法、ALA－D为比色法、ALA－P和ALA—U为高压液相色谱法。采用 CY．XJll．300台式血压计测定血压。对敏感人群的血样分离白细胞，提取DNA，通过特定引物，进行PCR扩增。凝胶电泳，与标准markers比较鉴别ALA－D基因型。采用SPSS10．0统计软件对上述实验结果进行统计分析，对各指标进行相应的ANOVA分析／检验、相关、回归分析《‘检验和多元回归分析。 结 果 调查研究结果表明：ALAD在血铅浓度为15－20pg／dl时开始出现有统计意义的下降、而 ALA－P人LA－U均在 20 pg／dl时出现显著上升。血铅与 LOG川 ALAD、LOG＊ALA－P和 LOG＊ALA－U相关系数分别是一0·893刀．853、0．867，直线回归方程为 y二 0．4055－0．olslX、y二 0．2748＋ 0．0221x、y二一03417 十0．olglx。血铅与＊和 Hb未表现有明显相关关系。血铅与空气铅之间有良好的相关关系，r＝0．802。空气铅与 LOG；／LAD。LOG＊LOG＊ALA－P、LOG＊ALA－U和Hi的相关系数分别为一0．778、0．725、0．760和一0．152，直线回归方程为 十二0．1155－0．6187x、＋＝0．6427＋0．7343x、y＝－0．0397＋0．6570x和 y＝47．5429－0．8279 x。SBP和 DBP在血铅浓度为40 pg／dl开始显著上升。血铅和空气铅与DBP的相关系数分别是 0．187和 0．191。舒张压达 ＞90nunHg时在血铅 ＞20ug／dL人群中发生率显著增加。采用 backward法进行多元回归分析表明，影响收缩压主 ·2·要因素是血铅、家族史和年龄；舒张压则是空气铅浓度、工龄、吸烟和饮酒。对选择的 11例敏感人群的 ALAD基因多态性分析未见有 ALADI－2和ALADZ上型基因携带者。 讨 论 末梢血红细胞ALAD的活性作为反映铅接触最敏感指标而广泛被采用。但它的血铅阈值尚无明确结论。我们调查的结果表明ALAD下降的阈值是在15－20收dl。在各种文献报道中这一数值处于中等水平。导致血铅阈值研究结果的不一致性，有可能通过分析调查对象、作业环境、实验方法和研究年代的差异得到解读。 铅损伤时叶琳代谢中间产物ALA在血液和尿中增加。我们采用较精确和特异的荧光高压液相色谱法得出ALA－P和ALA－U的血铅阈值均是20卜少d。我们测定的血铅阈值基本上是两个工厂人群血铅的分界。对于ALA－U而言，它与ALAD不同，血铅的阈值基本上存在于较高铅暴露环境的人群，而非对照人群。因为，ALA－U不仅是反映铅暴露，它的量的多少意味着铅对叶琳代谢影响的程度，是铅损伤的效应指标。在我们研究的对象中，有的名工人 ALA－U值大于或等于 6mg／L，更多还原

【Abstract】 PrefaceHuman beings have used lead for thousand years, along with it is lead intoxication. Because of its wild use, research of lead intoxication stills plays an important role in heavy metal toxicology.Producing conditions of lead are advancing as the development of science. Lacking of high - concentration lead environment makes the epidemic researches of developed countries pay more attention on healthy effect induced by lead of low -concentration. But in China, especially for small enterprises, the working condition is terrible, so the healthy risk caused by exposed to high - concentration lead can’t be ignored at all. Investigation of Shenyang Smelting Factory which technology is only equal to the early 70’slevel in developed countries, in-dicat that the lead concentration in working environment is very high. Workers in Shenyang Low - Pressure Switch Factory were studied as a group exposed to low - concentration lead, who were exposed the smoke from Smelting Factory. Though they didnt take part in the smelting work, they were worked in high -concentration air. This study is based on this background.Dose - effect relation can be seen in the early stage of lead intoxication, with the more exact and sensible analyzing methods. The revaluing the dose -effect relation between lead and porphyrin metablism is very important to defining the up - limit and diagnosis of " lead worker" and it is good for healthy care, healthy diagnosis and drafting healthy standards.We dont know exactly how much lead can effect blood pressure. China is under high - rate hypertension, and it is very important to prevent hypertensionfrom prevalence. Whether lead can cause hypertension still needs more evidences.Research of ALAD genetic polymorphism is the key - point of lead influence to porphyrin metablism, Also, it is another aspect of the sensitivty of human gene to occupational and environmental factor. This is important to definition of employees and high - risk group.Material and MethodsIn this research, we chose 150 workers from Smelting Factory and 70 workers from Switch Factory as object, all were males and average ages were 36. 00 ±1.31 and 33.54±8.49. The questionnaire were based on " Questionnaire of Worker Exposed to lead in Shenyang" , added some symptoms, medical record, family history, smoking history, drinking history, recuperation and chelating lead and health custom of worker in working places. We detected lead in blood, ALAD,ALA - P,ALA -U, Ht and Hb in 5ml peripheral blood. We also detected the blood pressure of the objects. As susceptive group we chose 11 low -blood - lead and larger decreasing ALAD values objects in 230 samples to analyze ALAD gene polymorphism.We used no - flame atom absorption spectrophotometer, colorimeter and HPLC to detect blood lead, ALAD, ALA - P and ALA - U, and used CY. XJl 1. 300 blood - Pressure meter to detect blood pressure, separated the WBC of sensible group, extracted DNA and then made PCR amplify by specific primer. We compared ALAD genotype to the standard marker after making gel - e-lectrophoresis, analyzed these results by SPSS10.0, then did ANOVA analyzed, t - test, correlation, regression, x2 ~test and multiple - regression.ResultsThe research indicated that ALAD had statistic decreasing when the lead concentration of blood was 15 -20μg/dl and ALA - P, ALA - U was at 20μg/dl, the concentration increased. Correlation coefficient of blood lead and LOG10 ALAD, LOG10ALA - P, and LOG10ALA - U are -0. 893,0. 853,0. 867. Its liner regression were y = 0. 4055 - 0. 018x, y = 0. 2148 + 0. 0221x, y = - 0. 3417 +0. 019Ix. But there was no obvious relationship between blood lead and Ht, Hb. Good correlation coefficient existed in blood lead and air lead, r=0. 802. Correlation coefficient of air lead and LOG10ALAD, LOGGIA - P, and LOG10ALA - U and Ht were - 0.778,0.725 ,0. 760 and - 0.152,liner regression regulation were y =00. 1155 -0. 6187x, y =0. 6427 +0.7343x, y = -0. 0397 +0.6570x and y =47. 5429 -0. 8279x. Obvious increasing SBP,更多还原