空气颗粒物对健康影响的研究进展
臧旭
沈阳军区总医院北陵临床部检验科,沈阳 110034 [摘要]空气污染物是由多种资源消耗途径产生的异质混合物,可以损伤人体健康,破坏自然环境。本文采用文献资料法,围绕空气颗粒物的类型、毒性作用特点及流行病学和实验室的研究情况,综述近年来国内外空气颗粒物对机体健康影响的研究,探讨作用机制,通过各方合力有效地控制空气污染继续加重的程度,更好地去理解和阐释空气颗粒物对人体的作用,利用前沿技术解决更多困扰临床治疗的难题。
[关键词]空气颗粒物;人体健康;影响
[Abstract]The air pollutants are foreign mixture produced by consumption of a variety of resources which can damage human health and destroy the natural environment.By searching on literature,this paper focused on type of the air pollutants,characteristics of toxic effect,epidemiology and experimental research which reviewed the study of the air pollutants on human health both home and abroad in recent years and explored its mechanism.It aimed parties to work together effectively control the degree of air pollution continues to grow and to better understand and at effectively controlling on continuing aggravation of air pollution,better understanding and clarifying the network of human by air pollutants,and solving plenty of problems existed in clinic by cutting-edge technology.
[Key words]Air particulate matter;Human health;Influence
空气污染物由室内和室外污染物组成,包括基本颗粒、气体成分有机复合物、部分农药(二辛类)和某些生物制品材料,当这些污染物进入呼吸系统时,就可能有潜在的毒性作用[1]。对人类的健康而言,颗粒混合物的成分是最主要的危险因素。针对空气颗粒物的研究不仅可成为相关疾病预防工作的基础,也可以更好地阐述受到空气污染后疾病的致病机制,并通过发现新的细胞反应,提高对细胞途径的理解,最终发展成新的、有效的预防和治疗疾病的手段。
1 空气污染颗粒物的类型和特点
广泛途径来源的空气污染颗粒物由不同类型的异质混合物所组成,按照空气动力学直径微米水平划分,环境中的颗粒物被分为总悬浮颗粒物(total suspended particle,TSP,空气动力学直径<100 μm)、粗颗粒物(coarse particles,PM10,空气动力学直径<10 μm)、细颗粒物 (fine particles,PM2.5,空气动力学直径<2.5 μm)、超细颗粒物(ultrafine particles,PM0.1,空气动力学直径<0.1μm)和纳米颗粒物(nanoparticles,空气动力学直径<0.05 μm)。
空气污染颗粒物中有些颗粒物成分能够诱导氧自由基的损伤和呼吸系统疾病,一般来说,PM10又称为可吸入颗粒物,可以在上呼吸道沉降,有时会被黏膜纤毛运动或咳嗽、喷嚏等机制清除,而PM2.5、PM0.1和纳米颗粒则有更多的机会到达肺实质[2]。与粗颗粒物相比,无论是在数量还是在表面积方面,细颗粒物和超细颗粒物都可以为颗粒物的毒性带来更明显的意义。一方面,小颗粒在数量上占有绝对的优势;另一方面,由于单位表面积的优势,小颗粒在单位体积的空气中占有更大的表面积,这使得颗粒物有更强的能力搭载金属和其他吸入成分,同时更能够增强空气颗粒物对肺相关毒性的作用[3]。
2 空气颗粒物毒性作用的特点
空气颗粒物毒性作用不仅与颗粒物的空气动力学直径和在肺泡的沉积能力有关,还与颗粒物的组成成分有相关性,因为空气颗粒物的很多组分都能使机体产生肺部炎症和氧自由基损伤。悬浮颗粒能够使哮喘、慢性阻塞性肺疾病及呼吸系统感染等肺相关疾病发生恶化,这在众多研究中已经得到证实[4-6]。
空气颗粒物含有的主要金属元素包括铬、钴、镍、锰、锌、钒、铜以及铁[7]。颗粒物中金属元素的存在与颗粒物激发氧自由基的能力呈现一定的因果关系,因此金属沉积和肺测量参数也有一定关系。当长期暴露于含不同金属元素的空气中时,一秒钟用力呼气量(forced expiratory volume in one second,FEV1)和用力肺活量(forced vital capacity,FVC)都会降低,如铅[8]、锰[9]、锌[10]、铁[11]。此外,类似肺组织纤维化的损伤效应也可以由镍[12]和钒[13]的沉积所导致。
多环芳香烃类(polycyclic aromatic hydrocarbon,PAH)和金属元素是空气颗粒物的主要组分,在颗粒物表面区域可以起到叠加和协同作用[14],具有很强的致癌能力,包括苯并蒽、苯并荧蒽、苯并芘等成分。PAH可以使DNA发生突变,甚至是癌变[15]。DNA的损伤过程也成为机体癌变的关键步骤,因此可以作为癌症风险的生物标志物。
有研究[16]显示,当空气颗粒物细菌裂解时,内毒素可以释放到作用的微环境当中,这导致成年和儿童哮喘患者症状加重,造成肺功能损伤。空气颗粒物中含有的内毒素一直是呼吸系统疾病发生、发展的风险因素之一[17]。
相关文献综述报道[18]确定了颗粒物组分与日常死亡率和入院率的相关性,通过相对危险系数可以评估PM2.5暴露的毒性作用,但是面对多种情况不同方式的暴露条件,在全世界范围内,无论是来源于室外的空气或是室内的燃料,评估PM2.5暴露都缺乏对空气颗粒物组分或是来源进行分化鉴定的更为详尽的数据[19]。
3 流行病学研究和实验室研究评估空气颗粒物对机体的影响
流行病学调查和实验研究已经证实,空气污染会导致呼吸系统疾病发生率及肺功能损伤的增加,空气污染会增加当地的入院率并且带来诸多对健康不利的后果,包括呼吸系统疾病的哮喘[20]、慢性阻塞性肺疾病[21]、呼吸系统感染[22]、肺癌[23],同样空气污染颗粒物会增加慢性心血管系统疾病的发病率和死亡率[24]。
在疾病和年龄范围内,基于23个广谱死亡病因,在全球范围内评估了PM2.5和日常死亡率及入院率的相关性,PM2.5含量增加10 mg/m3,死亡风险就会增加1.04%(95%CI,confidence interval,0.52%~1.56%)[25]。因呼吸系统疾病导致的死亡远远高于心血管疾病导致的死亡,比例为 1.51%(1.01%~2.01%)∶0.84% (0.41%~1.28%)。颗粒物成分存在异质性,因此为了评估不同地区异质性的差异需要做更进一步的研究,小样本研究也应该评估和量化PM2.5对健康带来的风险[26]。
有纵向研究[27]已经证实了空气污染物的暴露与成长期肺功能的降低有一定关系。在10~18岁的人群中,空气污染物的慢性暴露对肺功能的完善产生负面效应,同时FEV1会有显著的临床诊断意义。在儿童期暴露于高水平的空气污染物中会降低肺的功能[28]。在儿童和老年阶段,肺功能的降低与悬浮颗粒物的浓度相关[29-30]。实验研究[31]显示,吸入和滴灌颗粒物能使肺功能降低并产生炎症反应,同时可导致多形核细胞渗出和细胞因子释放。美国科学家做过一个评估,PM2.5浓度的降低可以减少一定的入院率,PM2.5浓度每减少3.9 μg/m3,将减少7978例需要入院治疗的患者,大约能够节约3.33亿美元[32],所以空气污染水平的下降,即使下降很低都会给公共健康带来非常积极的影响[33]。
随着下一代测序技术的应用,更多疾病治疗靶点的新的分子改变将会被发现,对基因组结构的鉴别,即基因表达水平的增加或降低可以说明样本中的表达改变情况,这将扩展对疾病的理解,也可以带动新的诊断和治疗技术[34]。下一代测序技术的发展对空气颗粒物的研究有很大的推动作用,高通量技术可以探究细胞功能,分析转录组、基因结构、基因变化并且可以用全视角透视复杂的生物系统。在癌症生物学、生物统计学、生物信息学、分子生物学和计算机科学的基础上,下一代测序技术对患者的治疗将会非常重要[35]。
4 展望
全球多地的研究已经表明,空气污染颗粒物不仅可以损伤人体的健康,而且会破坏人类赖以生存的自然环境。鉴于此,为保护生活环境和生态环境,保障人体健康,防治大气污染,环境保护部已批准将《环境空气质量标准》作为国家的环境质量标准,希望各方能够合力有效地控制空气污染继续加重的程度。
广大医学科技工作者将通过收集广泛的临床资料,合理设计动物实验,建立更为详尽的有关基因和各种相关转录因子的数据库,在空气污染颗粒物影响的基础上,分析其在人和动物细胞或是组织中的表达形式、作用特点及其相关性,并探究其在特异组织表达相关假定转录因子结合位点的重要作用,应用前沿技术解决更多困扰临床治疗的难题,在分子水平上为疾病的治疗提供更直接、更有价值的依据,为人类的生命健康做出新的、重大的贡献。
[参考文献]
[1]Kampa M,Castanas E.Human health effects of air pollution [J].Environ Pollut,2008,151(2):362-367.
[2]Duffin R,Mills NL,Donaldson K.Nanoparticles-a thoracictoxicology perspective[J].Yonsei Med J,2007,48(4):561-572.
[3]Tao F,Gonzalez-Flecha B,Kobzik L.Reactive oxygen species in pulmonary inflammation by ambient particulates[J].Free Radic Biol Med,2003,35(4):327-340.
[4]Shi JP,Evans DE,Khan AA,et al.Sources and concentration of nanoparticles (<10 nm diameter)in the urban atmosphere[J].Atmos Environ,2001,35(7):1193-1202.
[5]Braga AL,Saldiva PH,Pereira LA,et al.Health effects of air pollution exposure on children and adolescents in Paulo,Brazil[J].Pediatr Pulmonol,2001,31(2):106-113.
[6]Francesca D,Peng RD,Zeger SL,et al.Particulate air pollution and mortality in the United States:did the risks change from 1987 to 2000?[J].Am J Epidemiol,2007,166(8):880-888.
[7]Wilson MR,Lightbody JH,Donaldson K,et al.Interactions between ultrafine particles and transition metals in vivo and in vitro[J].Toxicol Appl Pharmacol,2002,184(3):172-179.
[8]Gurgueira SA,Lawrence J,Coull B,et al.Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation [J].Environ Health Perspect,2002,110(8):749-755.
[9]Bagci C,Bozkurt AI,Cakmak EA,et al.Blood lead levels of the battery and exhaust workers and their pulmonary function tests[J].Int J Clin Pract,2004,58(6):568-572.
[10]Boojar MM,Faranak G.A longitudinal follow-up of pulmonary function and respiratory symptoms in workers exposed to manganese[J].J Occup Environ Med,2002,44(3):282-290.
[11]Lagorio S,Forastiere F,Pistelli R,et al.Air pollution and lung function among susceptible adult subjects:a panel study[J].Environ Health,2006,5(4):1-12.
[12]Roemer W,Hoek G,Brunekreef B,et al.PM10 elemental composition and acute respiratory health effects in European children (PEACE project).Pollution Effects on Asthmatic Children in Europe[J].Eur Respir J,2000,15(3):553-559.
[13]Jinshun Z,Xianglin S,Vincent C,et al.Occupational toxicology of nickel and nickel compounds[J].J Environ Pathol Toxicol Oncol,2009,28(3):177-208.
[14]Pénard-Morand C,Charpin D,Raherison C,et al.Longterm exposure to background air pollution related to respiratory and allergic health in schoolchildren ISAAC[J].Clin Exp Allergy,2005,35(10):1279-1287.
[15]Bonner JC,Rice AB,Moomaw CR,et al.Airway fibrosis in rats induced by vanadium pentoxide[J].Am J Physiol Lung Cell Mol Physiol,2000,278(1):L209-L216.
[16]Srensen M,Autrup H,Mller P,et al.Linking exposure to environmental pollutants with biological effects[J].Mutat Res,2003,544(2-3):255-271.
[17]Thorne PS,Kulhankova K,Yin MR,et al.Endotoxin exposure is a risk factor for asthma:the national survey of endotoxin in United States housing[J].Am J Respir Crit Care Med,2005,172(11):1371-1377.
[18]Robert D,David M,Ken R,et al.Airborne endotoxin is associated with respiratory illness in the first 2 years of life [J].Environ Health Perspect,2006,114(4):610-614.
[19]Atkinson RW,Mills IC,Walton HA,et al.Fine particle components and health-a systematic review and meta-analysis of epidemiological time series studies of daily mortality and hospital admissions[J].J Expo Sci Environ Epidemiol,2015,25(2):208-214.
[20]Burnett RT,Pope CA 3rd,Ezzati M,et al.An integrated risk function for estimating the global burden of disease attributable to ambient fine particulate matter exposure[J]. Environ Health Perspect,2014,122(4):397-403.
[21]Ko FW,Tam W,Wong TW,et al.Effects of air pollution on asthma hospitalization rates in different age groups in Hong Kong[J].Clin Exp Allergy,2007,37(9):1312-1319.
[22]Ko F,Tam WT,Chan D,et al.Temporal relationship between air pollutants and hospital admissions for chronic obstructive pulmonary disease in Hong Kong[J].Thorax,2007,62(9):780-785.
[23]Mei L,Stieb DM,Yue C.Coarse particulate matter and hospitalization for respiratory infections in children younger than 15 years in Toronto:a case-crossover analysis[J].Pediatrics,2005,116(2):e235-e240.
[24]C Arden P,Burnett RT,Thun MJ,etal.Lung cancer,cardiopulmonary mortality,and long-term exposure to fine particulate air pollution[J].JAMA,2002,287(9):1132-1141.
[25]Chen H,Goldberg MS,Villeneuve PJ.A systematic review of the relation between long-term exposure to ambient air pollution and chronic diseases[J].Rev Environ Health,2008,23(4):243-298.
[26]Lim SS,Vos T,Flaxman AD,et al.A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions,1990-2010:a systematic analysis for the global burden of disease study 2010[J].Lancet,2012,380(9859):2224-2260.
[27]Atkinson RW,Kang S,Anderson HR,et al.Epidemiological time series studies of PM2.5 and daily mortality and hospital admissions:a systematic review and meta-analysis[J]. Thorax,2014,69(7):660-665.
[28]Horak F Jr,Studnicka M,Gartner C,et al.Particulate matter and lung function growth in children:a 3-yr follow-up study in Austrian schoolchildren[J].Eur Respir J,2002,19 (5):838-845.
[29]Gauderman WJ,Avol E,Gilliland F,et al.The effect of air pollution on lung development from 10 to 18 years of age [J].N Engl J Med,2004,351(11):1057-1067.
[30]Haidong K,Gerardo H,Rose KM,et al.Traffic exposure and lung function in adults:the atherosclerosis risk in communities study[J].Thorax,2007,62(10):873-879.
[31]Mccreanor J,Cullinan P,Nieuwenhuijsen MJ,et al.Respiratory effects of exposure to diesel traffic in persons with asthma[J].N Engl J Med,2007,357(23):2348-2358.
[32]Mazzoli-Rocha F,Fernandes S,Einicker-Lamas M,et al. Roles of oxidative stress in signaling and inflammation induced by particulate matter[J].Cell Biol Toxicol,2010,26 (5):481-498.
[33]Shah AS,Langrish JP,Nair H,et al.Global association of air pollution and heart failure:a systematic review and metaanalysis[J].Lancet,2013,382(9897):1039-1048.
[34]Seo JS,Ju YS,Lee WC,et al.The transcriptional landscape and mutational profile of lung adenocarcinoma[J].Genome Res,2012,22(11):2109-2119.
[35]Charles F,Trister AD,Erich H,et al.Impact of bioinformatic procedures in the development and translation of high-throughput molecular classifiers in oncology[J].Clin Cancer Res,2013,19(16):4315-4325.
Research progress of air particulate matter on health influence
ZANG Xu
Clinical Laboratory,Clinical Department of Beiling,the General Hospital of Shenyang Military,Shenyang 110034,China [中图分类号]R122
[文献标识码]A
[文章编号]1674-4721(2016)06(a)-0016-04
(收稿日期:2016-02-04 本文编辑:祁海文) |