【作者】 高知义；

【导师】 宋伟民；

【作者基本信息】 复旦大学 ， 劳动卫生与环境卫生学， 2010， 博士

【摘要】 大气细颗粒物(PM25)主要来源于石油、煤炭等化工染料的高温燃烧过程及机动车的尾气排放。当前,随着机动车数量的迅速增加以及多数化工污染企业搬离市区,机动车尾气逐渐成为影响城市空气质量的最主要污染来源之一。细颗粒物是机动车尾气中的主要有害成分,由于粒径小,比表面积大,吸附有大量有害物质如有机物多环芳烃、无机物、重金属及致病微生物等,可深入并沉积到深部肺组织,损害呼吸系统的健康,甚至可以穿过肺泡间质进入血液循环,对全身多个系统的健康造成危害。但是,我目前国尚未制定大气PM2.5的空气质量标准,不能满足改善城市空气质量及保护人群健康的需要。因此,加大对细颗粒物的相关基础性研究,为制定大气细颗粒物空气质量标准提供必要的科学资料,显得尤为重要和紧迫。鉴于此,本研究对上海市外勤交警和普通社区居民大气细颗粒的个体暴露状况及造成的健康损害进行探讨。基于城区大气细颗粒物主要来源于机动车尾气的特点,在研究中选择外勤交通警察作为细颗粒物的高暴露人群,社区居民作为细颗粒物的一般暴露人群,对两组人群的细颗粒物个体暴露情况进行为期1天的连续24h测定,比较两组人群细颗粒的个体暴露水平的差异,测定分冬季和夏季两次进行,并对研究人群的冬夏季细颗粒个体暴露水平进行比较。细颗粒物个体暴露水平的测定结果显示,冬季和夏季交警组对细颗粒暴露水平分别为115.4±46.2μg.m-3和86.8±41.4μg.m-3,居民对细颗粒暴露水平分别为74.9±40.1μg.m-3和59.7±34.3μg.m-3,交警组冬夏季个体细颗粒暴露水平均高于居民组；冬季和夏季个体细颗粒暴露水平相比较,两组人群冬季细颗粒的暴露水平均高于夏季,可能与冬季大气层结稳定,混合层高度低,大气扩散条件差,导致颗粒物在大气中累积所导致。另外,本测定结果与WHO和美国EPA PM2.5空气质量标准相比较,无论是交警组和居民组,细颗粒物的暴露水平均远高于上述标准,提示上海市大气细颗粒污染较为严重,从而会对健康产生不良影响。研究中,通过问卷详细调查了交警组和居民组的基本情况及健康自觉症状,发现交警组多种健康自觉症状如经常咳嗽、经常咳痰、咽部不适、鼻部不适、眼睛不适、视力下降、易怒及睡眠差等发生率均显著高于普通居民(P<0.05),提示交警健康受到损害,身体处于明显的亚健康状态。除此之外,本研究着重探讨了PM2.5暴露对人体心血管、呼吸系统和免疫系统的健康影响。在PM2.5对心血管系统健康影响的研究中,发现交警和居民的不正常心电图率分别为14.95%和5.94%,差异有统计学意义(P<0.05),提示交警的心脏健康可能受到影响；对于收缩压、舒张压和心率的异常发生率,交警组稍高于居民组,但两组之间差异无统计学意义；脉压差,交警组和居民组分别为41.65±8.38mmHg和38.14±6.91mmHg,交警组脉压差显著高于居民组(P<0.05)。尽管,交警组的脉压差尚不能被定义为脉压差增大,但已经超过了脉压差的正常范围(30-40 mmHg),预示心血管系统可能存在健康风险；对于心率变异性(HRV),时域指标SDNN和TV,交警组和居民组分别为46.89±14.02msec和71.48±32.78 msec,2219±1845 msec和3528±2549 msec,交警组两时域指标显著低于居民组(P<0.01)；频域指标LF、HF和LF/HF,交警和居民分别为33.02±12.42 msec2和30.61±9.59 msec2,15.73±5.92和25.43±13.02 msec2, 3.46±2.05和2.07±2.19 msec2,两组相比较,交警组HF降低,LF/HF升高,而LF两组无统计学差异(P>0.05)。在对PM2.5暴露与HRV参数相关及回归分析中,发现SDNN,HF和TV与PM2.5暴露水平呈负相关,LF/HF与PM2.5暴露水平呈正相关,LF与PM2.5暴露水平无明显相关。以上交警HRV指标的变化,提示交警组自主神经对心脏的调节能力降低,使心脏适应环境变化的能力减弱。在对免疫系统影响的研究中发现,交警组和居民组血液中WBC,NE,NE%,Ly,CD4+T/CD8+T相比较,差异无统计学意义(P>0.05),而Ly%(淋巴细胞比率),CD4+T细胞和CD8+T细胞,两组相比较差异具有统计学意义(P<0.01)；对于免疫球蛋白,交警组血清中IgM较居民组降低(P<0.05),而IgG则较居民组升高(P<0.05),IgA和IgE两组差异无统计学意义,表明机体免疫状态受到影响。对肺通气功能影响的研究中,交警组肺通气指标除PEF外,FVC、FEVl.0和FEV1.0/FVC％均比居民有所降低(P<0.05)。在肺通气指标与PM2.5暴露的相关及回归分析中发现,FVC和FEV1.0/FVC％与PM2.5暴露水平与存在负相关,PEF和FEV1.0/FVC％与PM2.5暴露水平无明显相关性。对交警按工龄分组,发现工龄是影响肺通气功能的因素之一；在PM2.5暴露致肺通气功能障碍的类型上,以限制通气功能障碍为主；表明长期暴露于高浓度PM2.5的污染环境是导致呼吸系统受损,通气功能下降的重要因素。另外,在对呼吸系统影响的研究中,还探讨了PM2.5对血清Clara细胞蛋白(CC16)和C反应蛋白(CRP)的影响。血清CC16具有抗炎、抗纤维化及活跃的增殖分化能力,参与支气管上皮损伤的修复过程,可敏感地反应气道上皮完整性,是评价呼吸道上皮屏障功能的早期敏感指标。CRP是一种典型的急性时相蛋白,参与机体许多重要的生理和病理反应,其浓度上升是炎症和组织损伤的敏感指标。本文对交警组和居民组血清中的CC16和CRP水平分别进行了测定,测定结果显示,交警组和居民组血清中CC16及CRP水平分别为10.05±5.31 ng/ml和12.64±4.53ng/ml,7.38±6.00μg/ml和5.60±4.04μg/ml,两组比较,差异均有统计学意义(P<0.05)。究其原因,可能是PM2.5暴露导致了呼吸道屏障功能受损,机体发生炎症反应或某种程度的损害。本研究还对PM2.5暴露致人体健康影响的效应生物标志物进行了探讨,结果发现肺通气功能指标中FVC和FEV1.0、心率变异性指标、血清CC16、CRP和免疫学指标CD4+T细胞和CD8+T,以及血清免疫球蛋IgM和IgG水平均与PM2.5暴露水平相关,且交警和居民相比,上述各指标差异有显著统计学意义,可作为PM2.5暴露致机体损伤的效应生物标志物。本文对PM2.5暴露导致上述健康问题中的遗传因素进行探讨。课题组在以前的研究中曾筛选出7种小鼠肺损伤易感基因,以此为基础,本研究通过同源基因查找,发现人体中的CXCL3、C4、C5、CP、CAP1、MAP2、NME7基因与上述小鼠的7种肺损伤易感基因属同源基因。研究中,对这7种基因进行测序,探讨其在人体PM2.5暴露影响肺通气过程中是否发挥遗传易感性作用。结果显示,MAP2基因2363位点处的G2363G基因型和C5基因3156位点处的A3156G基因型是细颗粒物致肺通气功能障碍的遗传易感性因素。对PM2.5暴露和基因的多态性在肺功能障碍发生中的交互作用进行探讨,发现MAP2基因2363位点的GG基因型和C5基因3156位点AG基因型与PM2.5暴露在肺通气功能障碍发生过程中存在交互作用。更多还原

【Abstract】 Atmospheric fine particulate matters (PM2.5) comes mainly from coal and oil high temperature combustion process and exhaust emissions from motor vehicles. Currently, as high-polluting chemical enterprises removed to suburban areas and the rapid increase in the number of motor vehicles, motor vehicle exhausts has become the key pollutant that affected the urban air quality. PM2.5 is one of the major harmful ingredients in vehicle exhaust pollution. Based on extremely small in size, PM2.5 can enter and deposit into the deep lung tissue, even cross the alveolar interstitial into the blood circulation. PM2.5 has large specific surface areas and adsorb large number of harmful substances, such as polynuclear aromatic hydrocarbons, heavy metals and pathogenic micro-organisms, so it can cause directly or indirectly damage to the respiratory health. In health assessment of air pollution, PM2.5 is often used as the landmark pollutant. Unfortunately, China has presently not yet developed fine particulate matter air quality standards and urban air quality monitoring system only limited to sulfur dioxide, nitrogen dioxide and inhalable particles (PM10), which can not meet to improve urban air quality and protection of human health. Therefore, it has become very necessary and impendency to increase the study of fine particulate matter. So, in this paper, we discussed on public health hazard of PM2.5 in Shanghai city.Based on the fact that fine particulate matter in urban air comes mainly from motor vehicle exhaust, field traffic policemen were recruited as PM2.5 higher exposure group and community residents as PM2.5 common exposure group. The level of PM2.5 exposure for traffic policemen and community residents were continuous 24h monitoring, which was respectively measured in winter and summer. The monitoring result showed that the levels of PM2.5 exposure in traffic policemen were higher than those in community residents, whether winter or summer. For two groups, the levels of PM2.5 exposure were both much higher than WHO and U.S. EPA air quality standards, which revealed that the fine particle pollution in air in Beijing was serious. Next, we carried a detailed inquiry into basic situation and subjective symptoms for traffic policemen and residents. The survey found that the incidence of a variety of symptoms in policemen were higher than those in residents, such as sputum, nasal discomfort, throat discomfort, decreased vision, eye discomfort, irritability and poor sleep etc., which showed that traffic police were in a distinct sub-healthy state, and Multiple organs were affected. In the paper, We focus on the effects of PM2.5 exposure on cardiopulmonary and immunological parameters, included pulmonary function, electrocardiogram, heart rate variability, immune cells and immune globulin, and so on. The findings confirmed that exposure to PM2.5 can lead to health hazards of cardiopulmonary and immune systems, and the extent of the damage was positively correlated with PM2.5 exposure concentration and duration.The research of biomarkers is a hot topic in the field of environmental occupational health, Which is considered as a milestone in the development of environmental medicine. There are three biomarkers, namely exposure, effect and susceptibility biomarkers. Among of them, the effect biomarkers contribute to early detection and diagnosis of the health hazards, take preventive measures as soon as possible. In this study, the effect biomarkers caused by fine particles exposure were discussed. It was found that the parameters such as FVC and FEV1.0, heart rate variability, CC16, CRP, CD4+T, CD8+T, IgM and IgG etc. were closely related to PM2.5 exposure. There was significant difference in above parameters between traffic policemen and residents. As is well known, for the occurrence of health problems, environmental factors and genetic factors were always interaction, can not be separated. Therefore, we explored the genetic factors in the health hazards. In the previous study, we has found that exposure to PM2.5, C57BL/6 mice was prone to lung injury than C3H/He mice, Showed that C57BL/6 mice had high sensitivity to lung injury exposed to PM2.5. In the follow-up gene chip experiment, seven kinds of lung injury susceptibility gene were found out in C57BL/6 mice. At present, genetic study has discovered that 99% of genes in human and mouse were homologous genes. Were there lung injury susceptibility gene in human body? By NCBI database, seven kinds of lung injury susceptibility gene (that was CXCL3, C4, C5, CP, CAP1, MAP2 and NME7) in human body were found, which are homologous genes with mice. Firstly, the seven genes were sequenced. Next, we analyzed sequencing results To clarify the role of these seven genes in human lung injury. In our research, we found that the genetic polymorphism of G2363G in MAP2 gene and A3156G in C5 gene played a role in lung ventilation dysfunction in human body. Further, the interaction between MAP2, C5 gene and PM2.5 exposure in human lung ventilation dysfunction was confirmed.更多还原