【作者】 黄坤；

【导师】 邬堂春；

【作者基本信息】 华中科技大学 ， 公共卫生， 2012， 硕士

【摘要】 中美两国最新死因调查结果显示，肺癌已经成为恶性肿瘤的首位死亡原因，心血管疾病则是目前致死率最高的疾病。流行病学研究发现，职业性多环芳烃（PAHs）暴露可以增加工人肺癌和心血管疾病的发病风险，同时有足够的证据表明肺癌和心血管疾病的病理类型、发病机制和易感性等方面均存在明显的性别差异，导致这些差异的具体机制尚不明确。探讨PAHs暴露致男女工人早期健康损伤效应的差异情况，可以为阐明这一机制提供新的线索和思路，进而为肺癌和心血管疾病防治的性别化提供理论依据。本研究选取某焦化厂330名不吸烟不喝酒工人作为研究对象，其中男性192人，女性138人。对工人日常工作环境中的PAHs进行检测；对工人进行健康体检并收集血样和尿样，使用气相色谱-质谱联用仪（GC-MS）测定尿中12种PAHs代谢物（OH-PAHs）的含量；使用高效液相色谱-电化学技术（HPLC）和酶联免疫试剂盒（ELISA）检测尿中8-OHdG和8-iso-PG浓度；采用胞质分裂阻滞微核实验（CBMN）检测个体遗传损伤水平；使用动态心电图检测仪测定工人10分钟动态心电图，分析正常连续的5分钟HRV指数：MN间期标准差（SDNN）、相邻NN间期差值的均方根（rMSSD）、低频（low LF）、高频（HF）和总功率（TP）。研究结果显示：按照不同作业区域分组后，低中高暴露区域女性工人的氧化损伤指标8-OHdG和8-iso-PG浓度均要高于男性，在低和中暴露区域差异具有统计学意义（P＜0.01）；女性工人的微核率水平同样在低中高暴露区域都要高于男性，在低和中暴露区域差异具有统计学意义（P＜0.05）；女性工人的HRV指数普遍低于男性，在中暴露区域女性HRV指数LF要显著低于男性（P＜0.05），在低暴露区域女性HRV指数HF要显著高于男性（P＜0.05），中和高暴露区域女性HRV指数LF/HF要显著低于男性（P＜0.05）。不同PAHs代谢物浓度三分位分组后，女性的8-0HdG和8-iso-PG浓度均要高于男性，8-0HdG浓度水平经由2-NAP、1-,2-,3-,4-,9-PHEN和2-FLUO三分位分组时，在低和中浓度水平显著高于男性（P＜0.05），经由1-NAP三分位分组时，在中和高浓度水平显著高于男性（P＜0.05），经由1-PRP和OH-PAHs总和三分位分组时，只在中浓度水平显著高于男性（P＜0.05）。女性的8-iso-PG经由1-NAP，1-,2-,4-,9-PHEN三分位分组时，在中浓度水平显著高于男性（P＜0.05），经由1-PRP和OH-PAHs总和三分位分组时，在高浓度水平显著高于男性（P＜0.05），经由2-NAP，2-FLUO和3-PHEN三分位分组时，在中和高浓度水平显著高于男性（P＜0.05）。女性的微核率在所有浓度水平都要高于男性。经由1-NAP和1-,9-PHEN三分位分组时，女性工人的微核率在低中高三个浓度水平均要显著高于男性（P＜0.05），经由2-NAP，9-FLUO和3-,4-PHEN三分位分组时，在低和中浓度水平显著高于男性（P＜0.05），经由1-PRP三分位分组时，只在中浓度水平显著高于男性（P＜0.05）经由2-PHEN，2-FLUO和OH-PAHs总和三分位分组时，只在低浓度水平显著高于男性（P＜0.05）；女性工人的OTM值在低和高浓度水平都要低于男性，但是差异并不具有统计学意义，在某些PAHs代谢物的中浓度水平，女性的OTM值要高于男性，意外的发现只有经由1-NAP三分位分组时，女性的OTM值在中浓度水平显著高于男性（P＜0.05）。女性工人的6种HRV指数几乎在所有浓度水平均要低于男性。经由2-NAP，1-,3-,9-PHEN和9-FLUO三分位分组时，女性HRV指数LF在中和高浓度水平显著低于男性（P＜0.05），经由1-NAP，1-PRP，2-PHEN和OH-PAHs总和三分位分组时，LF只在中浓度水平显著低于男性（P＜0.05），经由2-FLUO三分位分组时，LF只在高浓度水平显著低于男性（P＜0.05）；女性工人的HRV指数LF/HF经由1-,2-NAP，1-PRP，1-,2-,9-PHEN以及OH-PAHs总和三分位分组时，在中浓度水平显著低于男性（P＜0.05）。综上所述：1、在相同的作业区域，女性的氧化损伤和遗传损伤程度高于男性，心率变异性低于男性；2、在相似的PAHs代谢物浓度水平，女性的健康损伤程度仍然高于男性，心率变异性仍然低于男性。由此可见女性对于PAHs暴露要更敏感，可能更易感肺癌和心血管疾病。本研究的创新之处在于：1、从性别角度系统探讨PAHs暴露致焦炉工早期健康损伤效应的研究尚属首次；2、我们检测了焦化厂空气中16种PAHs浓度，并且检测了工人尿中12种PAHs代谢物浓度，精确地评价了工人的整体暴露水平。3、研究对象均为不吸烟不喝酒人群，排除了吸烟饮酒的干扰，提高了研究结果的可信度。本研究的不足之处在于：只是从整体角度上分析了PAHs致早期健康损伤的性别差异情况，校正了年龄、工龄和BMI等潜在影响因素，将来还有待对这些潜在因素进行更细更深层次的分析。更多还原

【Abstract】 According to the reports of death cause form China and American, lung cancer hasoccupied the first place of cancer death. The cardiovascular disease is the leading cause ofdisease death. Many epidemiologic studies have shown that occupational PAHs exposure isassociated with an increasing risk of lung cancer and cardiovascular disease. And therewere enough evidences which have proved that obvious sex differences of the pathologicaltypes, pathogenesis and the susceptibility existed in lung cancer and cardiovascular disease.But we have little knowledge about its mechanism. The investigation on the sex differencesof early healthy damage effects caused by PAHs exposure in the coke oven workers couldprovide new valuable ideas and clues to interpret this mechanism and theoretical basis forthe sex related prevention and treatment of Lung cancer and cardiovascular diseases.This study recruited330non-smoking and non-drinking workers （192males and138females）as the research objects in a coke oven plant. We done health examination for eachresearch object and collected their blood and urine samples.12kinds of PAHs metabolites（OH-PAHs）concentration were determined with gas chromatography-mass spectrometryto assess PAHs exposure. The levels of8-isoprostane and8-OHdG were determined withELISA and high performance liquid chromatography (HPLC) respectively, to assess lipid per-oxidation and oxidative DNA damage. The cytoplasm division block of the nuclearmethod is used to test CBMN in order to assessment the individual genetic damage level.Short-duration HRV indices including standard deviation of NN intervals (SDNN), rootmean square of successive differences in adjacent NN intervals (rMSSD), low frequency(LF), high frequency (HF) and total power (TP) from all subjects were determined with DelMar Medical systems.Firstly, the workers were divided into three exposure areas according to the distancesfrom their workplaces to the coke oven. Our results showed that the8-OHdG and8-iso-PGconcentration among female workers were higher than males in low, intermediate and highexposure areas with statistically significant (P<0.01) result in the low exposure areas andintermediate exposure areas. The micronucleus rate among female workers was lower thanmale in low, intermediate and high exposure areas with statistically significant (P<0.01)result in low and intermediate exposure areas. HRV index among female workers was lowerthan the most males, and LF among females was lower than males with statisticallysignificant (P<0.01) result only in intermediate exposure areas. HF among females washigher than males with statistically significant (P<0.01) result only in low exposure areas,LF/HF among females was lower than males with statistically significant (P<0.01) result inintermediate and high exposure group areas.Secondly, the workers were divided into three concentration groups by trisections ofeach individual OH-PAHs and ΣOH-PAHs. Our results showed that8-OHdG and8-iso-PGconcentration among the females were higher than males in all concentration groups. The8-OHdG concentration among female workers was higher than males with statisticallysignificant (P<0.01) result in T1and T2concentration groups trisections by2-NAP,1-,2-and3-,4-,9-PHEN and2-FLUO. Females was higher than males with statistically significant(P<0.01) result in T3concentration groups trisections by1-NAP. Females was higher thanmales with statistically significant (P<0.01) result in T2concentration groups trisections by 1-PRP and ΣOH-PAHs. The8-iso-PG concentration among female workers was higher thanmales with statistically significant (P<0.01) result in T2concentration groups trisections by1-NAP,1-,2-,4-,9-PHEN.The micronucleus rate among female workers was higher than males in allconcentration groups. Female workers was higher than males with statistically significant(P<0.01) result in all of the concentration groups trisections by1-NAP and1-,9-PHEN.Female workers was higher than males with statistically significant (P<0.01) result in T1andT2concentration groups trisections by2-NAP,9-FLUO and3-,4-PHEN. Female workerswas higher than males with statistically significant (P<0.01) result in T1concentration grouptrisections by2-PHEN，2-FLUO and ΣOH-PAHs.The OTM value among female workers was lower than males in almost all theconcentration groups. The OTM value among female workers was higher than males withstatistically significant (P<0.01) result in T2concentration groups trisections by1-NAP.The HRV index among females was lower than male in almost all concentration groups.The LF among female workers was lower than males with statistically significant (P<0.01)result in T3concentration groups trisections by2-NAP,1-,3-,9-PHEN and9-FLUO.Female was lower than males with statistically significant (P<0.01) result in T2concentration groups trisections by1-NAP,1-,2-PHEN,1-PRP, and ΣOH-PAHs. Femalewas lower than males with statistically significant (P<0.01) result in T3concentration groupstrisections by2-FLUO. The LF/HF among female workers was lower than males in T2concentration groups trisections by1-,2-NAP,1-PRP,1-,2-,9-PHEN and ΣOH-PAHs.In conclusion, the oxidative and genetic damage among females were more serious thanmales. Females were more sensitive than males in PAHs exposure. And females may bemore susceptible to lung disease and heart disease.There are a number of strengths in this study. First, this is the first epidemiologicstudy to investigate the sex differences of the early healthy damage effects caused by polycyclic aromatic hydrocarbons exposure in coke oven workers. Second, we determinedten urinary OH-PAHs to assess PAHs exposure, which provided accurate PAHs exposure.And the research objects is non-smoking and non-drinking workers, which will increase thecredibility of the study. There are also some limitations in the study. The analysis of therelevant indicators between male and female is conducted with adjusting potentialinfluence factors of age, working years and BMI. These potential factors are moresignificance to analyze in the future.更多还原