Article(id=1320438091643470260, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1320438006813672182, articleNumber=null, orderNo=null, doi=10.11847/zgggws1146564, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1733241600000, receivedDateStr=2024-12-04, revisedDate=1740067200000, revisedDateStr=2025-02-21, acceptedDate=1754841600000, acceptedDateStr=2025-08-11, onlineDate=1792746573600, onlineDateStr=2026-10-23, pubDate=1773072000000, pubDateStr=2026-03-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792746573600, onlineIssueDateStr=2026-10-23, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792746573600, creator=13701087609, updateTime=1792746573600, updator=13701087609, issue=Issue{id=1320438006813672182, tenantId=1146029695717560320, journalId=1319373219989389464, year='2026', volume='42', issue='3', pageStart='257', pageEnd='384', issueExtLink='null', onlineDate='null', pubDate='1773072000000', pubDateStr='2026-03-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1792746553376, creator='13701087609', updateTime=1792748100383, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1320444495519404406, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1320438006813672182, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1320444495519404407, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1320438006813672182, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=375, endPage=379, ext={EN=ArticleExt(id=1320438091853185461, articleId=1320438091643470260, tenantId=1146029695717560320, journalId=1319373219989389464, language=EN, title=Research progress in effects of exposure to polycyclic aromatic hydrocarbons on thyroid function: a review, columnId=1320427713148597230, journalTitle=Chinese Journal of Public Health, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Currently, the incidence of thyroid diseases is high around the world and that of thyroid cancer is increasing year by year. Thus, there is an urgent need to take preventive measures. It is reported that exposure to environmental chemicals is a major risk factor for thyroid diseases. Polycyclic aromatic hydrocarbons (PAHs) are a class of semi-volatile organic pollutants that persist in environments such as water, atmosphere, and food. PAHs have been shown to be closely related to thyroid dysfunction. This article systematically summarized the toxicological and epidemiological studies about the effects of exposure to PAHs on thyroid function, as well as the potential mechanisms of thyroid function damage induced by PAHs. It is expected to provide a scientific basis for clarifying the hazard of PAHs to the thyroid function, reducing the burden of thyroid diseases, and revealing the pathogeneses of thyroid diseases.

, authors=Bin ZHOU1, Qiang ZENG2, Pingxia XIANG1, Ting YAO1, Rui HU1, Jinjun LUO3, authorsList=Bin ZHOU, Qiang ZENG, Pingxia XIANG, Ting YAO, Rui HU, Jinjun LUO, authorCompany=null, correspAuthors=Jinjun LUO, authorNote=null, correspAuthorsNote=
LUO Jinjun, E-mail:
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目前,世界范围内人群甲状腺疾病发病率高,甲状腺癌逐年增加,迫切需要从源头采取预防措施。研究表明,暴露环境污染物是甲状腺疾病发生发展的重要风险因素。多环芳烃(PAHs)是一类持久存在于水体、大气、食品等环境介质中的半挥发性有机污染物。已发现暴露PAHs与甲状腺功能异常密切相关。本文系统阐述PAHs暴露对甲状腺功能影响的动物实验和流行病学证据以及致甲状腺功能损伤的作用机制,为明确PAHs对甲状腺功能的危害、减轻甲状腺疾病负担以及甲状腺发病机制研究提供参考依据。

, authors=周斌1, 曾强2, 向萍霞1, 姚婷1, 胡睿1, 骆金俊3, *, *, authorsList=周斌, 曾强, 向萍霞, 姚婷, 胡睿, 骆金俊, authorCompany=null, correspAuthors=骆金俊, authorNote=

周斌(1986—),副主任技师,博士,研究方向:环境流行病学

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骆金俊,E-mail:
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多环芳烃暴露对甲状腺功能影响研究进展
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周斌 1 , 曾强 2 , 向萍霞 1 , 姚婷 1 , 胡睿 1 , 骆金俊 3, *, *
中国公共卫生 | 综 述 2026,42(3): 375-379
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中国公共卫生 |综 述 2026 , 42 (3) : 375 -379
多环芳烃暴露对甲状腺功能影响研究进展
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周斌1, 曾强2, 向萍霞1, 姚婷1, 胡睿1, 骆金俊3, *, *
作者信息
  • 1华中科技大学同济医学院附属武汉儿童医院(武汉市妇幼保健院),武汉 430014
  • 2华中科技大学同济医学院公共卫生学院,武汉 430030
  • 3湖北省疾病预防控制中心,武汉 430079
通讯作者:
骆金俊,E-mail:
作者简介:

周斌(1986—),副主任技师,博士,研究方向:环境流行病学

Research progress in effects of exposure to polycyclic aromatic hydrocarbons on thyroid function: a review
Bin ZHOU1, Qiang ZENG2, Pingxia XIANG1, Ting YAO1, Rui HU1, Jinjun LUO3
Affiliations
  • 1Wuhan Children′s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430014, China
  • 2School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China
  • 3Hubei Provincial Center for Disease Control and Prevention, Wuhan 430079, China
  • Corresponding Author:
    LUO Jinjun, E-mail:
出版时间: 2026-03-10 doi: 10.11847/zgggws1146564
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目前,世界范围内人群甲状腺疾病发病率高,甲状腺癌逐年增加,迫切需要从源头采取预防措施。研究表明,暴露环境污染物是甲状腺疾病发生发展的重要风险因素。多环芳烃(PAHs)是一类持久存在于水体、大气、食品等环境介质中的半挥发性有机污染物。已发现暴露PAHs与甲状腺功能异常密切相关。本文系统阐述PAHs暴露对甲状腺功能影响的动物实验和流行病学证据以及致甲状腺功能损伤的作用机制,为明确PAHs对甲状腺功能的危害、减轻甲状腺疾病负担以及甲状腺发病机制研究提供参考依据。

多环芳烃  /  甲状腺疾病  /  甲状腺癌  /  环境污染物

Currently, the incidence of thyroid diseases is high around the world and that of thyroid cancer is increasing year by year. Thus, there is an urgent need to take preventive measures. It is reported that exposure to environmental chemicals is a major risk factor for thyroid diseases. Polycyclic aromatic hydrocarbons (PAHs) are a class of semi-volatile organic pollutants that persist in environments such as water, atmosphere, and food. PAHs have been shown to be closely related to thyroid dysfunction. This article systematically summarized the toxicological and epidemiological studies about the effects of exposure to PAHs on thyroid function, as well as the potential mechanisms of thyroid function damage induced by PAHs. It is expected to provide a scientific basis for clarifying the hazard of PAHs to the thyroid function, reducing the burden of thyroid diseases, and revealing the pathogeneses of thyroid diseases.

polycyclic aromatic hydrocarbons  /  thyroid  /  exposure  /  toxicological research
周斌, 曾强, 向萍霞, 姚婷, 胡睿, 骆金俊. 多环芳烃暴露对甲状腺功能影响研究进展. 中国公共卫生, 2026 , 42 (3) : 375 -379 . DOI: 10.11847/zgggws1146564
Bin ZHOU, Qiang ZENG, Pingxia XIANG, Ting YAO, Rui HU, Jinjun LUO. Research progress in effects of exposure to polycyclic aromatic hydrocarbons on thyroid function: a review[J]. Chinese Journal of Public Health, 2026 , 42 (3) : 375 -379 . DOI: 10.11847/zgggws1146564
甲状腺是人体重要的内分泌器官,其分泌的甲状腺激素是维持胎儿生长发育不可缺少的激素,特别是对骨骼和脑部的发育尤为重要[1];同时也是新陈代谢、生长发育的重要调节因子,在心血管、骨骼和神经系统中均发挥重要作用[2-3]。此外,妊娠期甲状腺激素异常也与产科并发症如妊娠期高血压、胎盘早剥、流产密切相关[4]。调查资料显示,甲状腺疾病已成为仅次于糖尿病的妊娠期第二常见内分泌疾病,妊娠妇女甲状腺功能减退症和甲状腺功能亢进发病率约为0.3%~0.5%和0.1%~1%,而亚临床甲状腺功能减退症患病率高达4%~17%[5]。近年来,成年人甲状腺疾病发病率也呈上升趋势,患病率高达37.15%[6],全球甲状腺癌发病率约为5/10万[7-9]。多环芳烃(polycyclic aromatic hydrocarbons, PAHs)是一类持久存在于水体、大气、食品等环境介质中的内分泌干扰物。它主要经化石燃料等有机材料的不完全燃烧而形成。汽车尾气、冶炼生产、垃圾焚烧为主要污染源,PAHs排放至空气中后进一步沉降,导致食物和水源的污染。其次,不恰当的烧烤、熏制等烹饪方式也有助于PAHs形成。人群主要通过饮食摄入和空气吸入受污染的环境介质而广泛暴露于PAHs[10]。PAHs进入人体后通过模拟或干扰内源性激素和(或)内分泌激素受体,从而对包括甲状腺功能在内的内分泌系统造成不良影响[11-12]。本文系统阐述了PAHs暴露对甲状腺功能影响的动物实验和流行病学证据以及致甲状腺功能损伤的作用机制,为明确PAHs对甲状腺功能的危害、减轻甲状腺疾病负担以及甲状腺发病机制研究提供参考依据。
PAHs进入人体后在肝脏代谢酶作用下,可快速代谢为单羟基代谢物(monohydroxy-polycyclic aromatic hydrocarbons, OH-PAHs)。目前流行病学研究中多以尿液或血清中OH-PAHs作为PAHs暴露的生物标志,也有少量研究用原型作为暴露标志物[13]。有研究报道,菲的羟基代谢产物如1,9羟基菲、3–羟基菲等比其原型具有更高的毒性[14]。因此,在选择PAHs暴露生物标志时可适当考虑毒性差异。在众多的OH-PAHs中通常有4~10种产物可检出,对于四环及以上的PAHs代谢产物主要在粪便中排泄,所以3–羟基䓛、6–羟基䓛以及9–羟基苯并[a]芘这类含四环的OH-PAHs在尿液和血清中检出率都比较低,在关联分析中一般未纳入研究。此外,PAHs也可以通过胎盘屏障,在脐血和胎盘中检出,用于新生儿生命初期的暴露评估。已有研究表明,脐带血中多种PAHs浓度[菲、芘、二苯并呋喃、荧蒽、二苯并噻吩等)高于母血[15-16]。
目前的流行病学研究主要探讨PAHs暴露与甲状腺激素之间的关系,对其与甲状腺疾病之间关联研究较少,而且多以横断面研究为主,前瞻性队列研究较少[13, 17]。一项在伊朗进行的前瞻性队列研究(n=126)发现,孕妇(孕周24~32周)血清中二氢苊、芴、菲和总PAHs可降低3~5 d新生儿足跟血中促甲状腺激素(thyroid hormone, TSH)水平,其中二氢苊下降效果最明显[13]。另一项在中国太原市进行的队列研究发现,待产孕妇(孕周>35周)尿总PAHs代谢产物与脐血中三碘甲状腺原氨酸(triiodothyronine, T3)呈负相关[17]。在横断面研究中,研究结果不完全一致[18-21]。例如,在广州市3个区通过分层抽样方式招募学龄前儿童(n=590),发现尿总OH-PAHs与甲状腺体积呈正相关[18]。在基于伊朗儿童和青少年的研究中发现,尿1–羟基萘(1-hydroxynapthalene, 1-OHNap)、2–羟基萘(2-hydroxynapthalene, 2-OHNap)、1–羟基芘(1-hydroxypyrene, 1-OHPyr)和9–羟基菲(9-hydroxyphenanthrene, 9-OHPh)与TSH呈正相关[19]。在中国南京市辅助生殖男性人群中(n=480)发现2–羟基芴( 2-Hydroxyfluorene, 2-OHFlu)与TSH正相关[20]。但是在2015—2017年韩国国家环境健康调查的成年男性人群中(年龄≥19岁,n=1254)仅发现尿1-OHPyr与总三碘甲状腺原氨酸(Total triiodothyronine, TT3)呈负相关,未发现与TSH的显著性关联[21]。在中国(n=1645)和美国(n=1355,年龄>20岁)国家健康和营养调查中,发现女性尿1-OHPyr与TT3呈正相关[22-23]。课题组前期在育龄期男性人群中通过测定双份尿样10种OH-PAHs(1/2/3/4/9-OHPh、1/2-OHNa、2-OHFlu、9-OHFlu和1-OHPyr)以期提高个体暴露评估准确性,发现1-OHNa与TSH,1/9-OHPh与FT3, 2/3/9-OHPh和 ΣOHPh与游离甲状腺素(free thyroxine, FT4)呈负相关;此外,还发现OH-PAHs联合暴露与甲状腺激素[TSH,游离三碘甲状腺原氨酸(free triiodothyronine, FT3)和FT4]呈负相关性,其中1-OHNap,9-OHPh和2-OHPh分别在TSH,FT3和FT4负相效应中贡献最大[24]。造成流行病学结果不一致的可能影响因素包括:(1)研究设计类型和研究对象PAHs暴露水平不同;(2)人群特征和暴露检测指标存在差异;(3)研究样本量不同;(4)忽略了PAHs的联合效应[25]。流行病学研究还发现,PAHs对甲状腺功能影响存在性别差异[21-22]。例如,韩国的研究中,仅发现男性1-OHPyr与TT3呈负相关,而在女性中无此相关性[21]。2007—2008年美国国家健康和营养调查中发现,PAHs暴露主要影响女性TT3和男性FT4;女性(n=615)尿液中2-OHNap、2-OHPh和1-OHPyr水平与TT3水平呈正相关,而在男性中无此相关性;男性(n=740)尿液中1-OHPh、2-OHPh和9-OHFlu水平与FT4水平呈负相关,而在女性中无此相关性[23]。在中国国家健康和营养调查(男n=836;女n=809)中,发现男性2-OHFlu与TT3呈正相关,在女性中也有此相关性,还发现9-OHFlu、2-OHPh、1-OHPyr也与TT3呈正相关,2-OHNap、2-OHFlu和9-OHFlu与FT3呈正相关;在男性人群中发现1-OHNap与FT4呈正相关,而在女性中却仅发现2-OHFlu与FT4呈正相关[22]。性别差异可能一方面与甲状腺激素和性激素有关,女性暴露PAHs比男性更容易引起染色体损伤和氧化应激[12];另一方面可能与3个环的2-OHFlu和2-OHPh呈现部分雌激素活性有关[12],它的结构特征和雌激素活性使女性中2-OHFlu和2-OHPh与TT3或FT3显著相关。
甲状腺实质主要由许多甲状腺滤泡组成,滤泡上皮细胞有合成、储存和分泌甲状腺激素的功能。目前,PAHs对甲状腺功能影响的动物实验主要集中在苯并芘、芘和菲3种PAHs,其可改变甲状腺结构,影响甲状腺激素合成[26-29]。如Lao Q F等 [26]研究表明,苯并芘染毒大鼠滤泡上皮细胞坏死进入滤泡腔,少量滤泡腔内可见胶质细胞,表明苯并芘可损伤大鼠甲状腺结构。Movahedinia A等[30]研究发现,苯并芘染毒(2、10、25 mg/kg·bw)鲻鱼1、2、4、7、14 d,导致血浆TSH显著增高,第4天达到最高,而血浆T3和四碘甲腺原氨酸(Thyroxine, T4)显著降低,其滤泡上皮细胞明显降低,滤泡增大,有鳞状上皮的甲状腺滤泡细胞增加,说明甲状腺分泌活性降低。
在鱼类[28, 31]或大鼠[32]研究中也观察到相似的PAHs致T3和(或)T4降低的结果(100 μg/mL 芘,染毒35 d;0.5~50 nmol/L 芘,染毒岩石鱼胚胎5 d;10 mg/kg 苯并芘,染毒15 d)。Wu L Y等[33]研究发现,菲染毒斑马鱼胚胎7 d后(0.1 μg/L),显著降低T4水平,但增加T3浓度。然而,Zhong L Q等[29]研究发现,菲染毒4月龄成年斑马鱼2个月,雄性和雌性斑马鱼体内T4(85 μg/L菲)和T3(8.5 μg/L菲)均显著下降。此外,De Sandro V等[34]研究显示,大鼠染毒3–甲基胆蒽也可降低T4和T3,并负反馈调节TSH增加。Teles M等[35]研究发现,欧洲鳗鲡鱼染毒β–萘黄酮(2.7 μmol/L)2~3 d后显著降低血浆T4 水平,但对TSH和T3影响不大。
近年来,也有毒理学研究探讨了多种PAHs同时暴露对甲状腺功能的影响。例如,雌性大鼠每周口服3次13种PAHs混合物[萘、芴、菲、蒽、荧蒽、芘,䓛,苯并蒽,苯并芘,苯并(b)荧蒽,苯并(k)荧蒽,茚并(1,2,3-cd)芘,二苯并(a, h)蒽)],持续90 d,可以降低T3和T4水平[36]。此外,毒理学实验还表明,低剂量18种卤代芳香烃(2种二恶英、4种二苯并呋喃和12种多氯联苯)对甲状腺激素的联合作用表现为相加作用,而高剂量则表现为协同作用[37]。
有关PAHs致甲状腺功能改变的作用机制尚不完全清楚。已有研究表明,PAHs和/或OH-PAHs可能干扰甲状腺激素受体(thyroid hormone receptor, TR)[38-39]、甲状腺素转运蛋白(Transthyretin, TTR)[39]、下丘脑–垂体–甲状腺轴(hypothalamus-pituitary-thyroid, HPT)[27]和参与甲状腺激素合成酶[甲状腺过氧化物酶(thyroperoxidase, TPO)][40-41]。
典型的TR包括转录因子TRα、TRβ1和TRβ2。甲状腺激素与TR结合之后,受体诱导甲状腺激素发挥其正常的生理作用,影响蛋白质或者酶的合成。Sun H等[38]研究显示,1-OHNap和2-OHNap对TRβ受体具有拮抗剂活性,在体外抑制TRβ受体介导的转录。菲和芘分别染毒岩石鱼胚胎和斑马鱼,均抑制其甲状腺激素受体基因(TRα和TRβ)[29, 31]。Bekki K等[39]研究显示,7种2~4个环的酮类和醌类PAHs衍生物(25 μmol/L,苯并[c]菲[1, 4]醌,1,4–屈醌, 1,4–萘醌, 1–羟基–9–芴酮, 4,4′–二羟基联苯, 1-OHPh, 4-OHPh, 9-OHPh)对TTR表现出结合活性,其中苯并[c]菲[1, 4]醌结合活性最强,达90%;而且醌类和酮类衍生物TTR结合活性比羟基类衍生物强。
HPT轴的正反馈和负反馈调节甲状腺激素的稳态。研究表明,PAHs通过HPT调节甲状腺发育、甲状腺激素合成、受体和甲状腺素结合蛋白相关基因表达而影响甲状腺激素水平。如斑马鱼胚胎短期暴露苯并芘下调调节因子(trh和tshba)和甲状腺激素合成标志物(tg和nis)表达,抑制甲状腺滤泡上皮细胞成熟和甲状腺激素合成,导致甲状腺功能减退症[27]。芘和菲分别染毒岩石鱼胚胎和斑马鱼均抑制甲状腺原基发育相关基因(pax2.1、nkx2.1 a或pax8),下调甲状腺功能相关基因(Deio1/2和Ttr)表达,甚至影响甲状腺球蛋白基因(tg),导致T4和(或)T3浓度降低[29, 31]。β–萘黄酮染毒欧洲鳗鲡鱼通过干扰HPT显著降低血浆T4水平[35]。另外,HPT轴在降低甲状腺激素时可能存在性别差异,如菲染毒4月龄成年斑马鱼,在雄性斑马鱼中nis基因和TRα基因表达上调,而在雌性中下调或不变[29]。
TPO是富含血红素的糖蛋白,在甲状腺激素合成过程中催化碘向甲状腺球蛋白的转移。研究表明,苯并芘可通过抑制TPO的活性来影响甲状腺激素的合成[40]。正常情况下,TPO以220~240 kDa的二聚体形式存在,当它被转变为110 kDa的单体形式时,其活性可能降低[40]。此外,Zhong L Q等[29]研究显示,菲染毒斑马鱼抑制甲状腺过氧化物酶基因(tpo)表达。
PAHs已造成人群广泛暴露。作为一类典型的环境内分泌干扰物,其长期暴露对甲状腺功能甚至甲状腺疾病的影响值得关注。尽管目前已有毒理学和流行病学研究探讨了PAHs暴露对甲状腺功能的影响及作用机制,但仍有以下问题有待解决。首先,目前关于PAHs对甲状腺影响主要集中在单一种类的PAHs,而机体是持续复合低剂量暴露于PAHs。因此,很难将甲状腺损害效应归于某单一PAHs。未来应该聚焦环境水平PAHs联合染毒的毒理学研究以及PAHs混合暴露的流行病学研究。其次,目前流行病学研究多以横断面研究为主,无法确定PAHs与甲状腺功能异常的因果关系。因此,将来需要多开展前瞻性的队列研究,系统评估PAHs对不同性别和年龄人群甚至跨代人群的甲状腺功能影响。第三,目前的流行病学研究主要关注PAHs暴露与甲状腺激素之间的关系,未来更多需要开展PAHs暴露与甲状腺疾病,如甲状腺功能减退症、甲状腺功能亢进以及甲状腺肿瘤等之间的研究。最后,关于PAHs致甲状腺功能损害的具体作用机制尚未完全阐明,未来的研究可借助多种组学技术如表观遗传组、转录组、蛋白质组、代谢组等深入探讨具体的分子机制。

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2026年第42卷第3期
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doi: 10.11847/zgggws1146564
  • 接收时间:2024-12-04
  • 首发时间:2026-10-23
  • 出版时间:2026-03-10
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  • 收稿日期:2024-12-04
  • 修回日期:2025-02-21
  • 录用日期:2025-08-11
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作者信息
    1华中科技大学同济医学院附属武汉儿童医院(武汉市妇幼保健院),武汉 430014
    2华中科技大学同济医学院公共卫生学院,武汉 430030
    3湖北省疾病预防控制中心,武汉 430079

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骆金俊,E-mail:
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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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