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吸入胍类消毒剂致肺损伤的毒性特征及机制研究进展
作者:唐敬龙 祝肖肖 郑玉新

摘要:

聚六亚甲基胍(polyhexamethylene guanidine, PHMG)是一种具有广谱抗菌作用的高分子胍类化合物。自从韩国"加湿器消毒剂中毒事件"后,其呼吸毒性开始受到关注。韩国流行病学调查发现,家居中含有PHMG的消毒剂是引起肺纤维化的重要危险因素。动物实验研究结果显示,通过呼吸道暴露PHMG后会引起肺部发生不可逆的纤维化改变。TGF-β信号通路、上皮-间充质转化以及肺部炎症反应可能是介导PHMG引起肺纤维化的主要途径。本文概览综述了PHMG人群暴露特征及引起呼吸毒理学的研究进展,并结合我国实际使用情况,提出使用建议和警示,为合理规范使用PHMG相关产品提供建议。

关键词:肺纤维化;肺;毒性作用;聚六亚甲基胍;消毒剂

Abstract:

Polyhexamethylene guanidine (PHMG) is a high molecular guanidine compound with a broad spectrum of antibacterial effects. Since the outbreak of the 'humidifier disinfectant-induced lung injury’ event in South Korea, the respiratory toxicity of PHMG had become a public concern. An epidemiological survey in Korea found that PHMG-containing disinfectants were an important risk factor for pulmonary fibrosis. Animal experiments also showed that the exposure to PHMG through the respiratory tract could cause irreversible fibrosis in the lungs. TGF-β signaling pathway, epithelial-mesenchymal transition and pulmonary inflammation might be the main pathways that could mediate PHMG-induced pulmonary fibrosis. This article provided an overview of the characteristics of population exposure to PHMG and research progress in the field of respiratory toxicology and recommendations for the rational and standard of using PHMG-related products in China.

Key words: Pulmonary fibrosis;Lung;Toxic actions;Polyhexamethyleneguanide;Disinfectant

发表日期:2020/2

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参考文献:

[1]赵宇,王东黎.常见化学消毒剂特点及在铁路站车的应用[J].铁路节能环保与安全卫生,2018,8(2):96-99,112.
[2]崔树玉,陈璐.胍类消毒剂及其研究进展[J].中国消毒学杂志, 2011, 28(6): 749-751.
[3]OhH, KimCY, RyuB, et al. Respiratory Toxicity of Polyhexamethylene Guanidine Phosphate Exposure in Zebrafish[J]. Zebrafish, 2018,15(5):460-472. DOI: 10.1089/zeb.2018.1571.
[4]张玮,赵艳敏,于锋.聚六亚甲基胍消毒剂对海产养殖动物的毒性试验研究[J].医学动物防制,2007,23(3):172-174. DOI: 10.3969/j.issn.1003-6245.2007.03.007.
[5]AleshinaEY, YudanovaITN, SkokovaIF. Production and properties of polyvinyl alcohol spinning solutions containing protease c and polyhexamethylene guanidine [J]. Fibre Chemistry, 2001, 33(6): 421-423. https://doi.org/10.1023/A:1015039328620.
[6]Asiedu-GyekyeIJ, MahmoodSA, AwortweC, et al. A preliminary safety evaluation of polyhexamethylene guanidine hydrochloride[J]. Int J Toxicol, 2014,33(6):523-531. DOI: 10.1177/1091581814553036.
[7]OstapenkoYN, BrusinKM, ZobninYV, et al. Acute cholestatic liver injury caused by polyhexamethyleneguanidine hydrochloride admixed to ethyl alcohol[J]. Clin Toxicol (Phila), 2011,49(6):471-477. DOI: 10.3109/15563650.2011.592837.
[8]ParkJ, LeeH, ParkK. Eye irritation tests of polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a tissue model of reconstructed human cornea-like epithelium[J]. Environ Health Toxicol, 2019,34(2):e2019004. DOI: 10.5620/eht.e2019004.
[9]KimEH, AhnK, CheongHK. Use of humidifiers with children suffering from atopic dermatitis[J]. Environ Health Toxicol, 2012,27:e2012004. DOI: 10.5620/eht.2012.27.e2012004.
[10]KimHJ, LeeMS, HongSB, et al. A cluster of lung injury cases associated with home humidifier use: an epidemiological investigation[J]. Thorax, 2014,69(8):703-708. DOI: 10.1136/thoraxjnl-2013-204132.
[11]KimKW, AhnK, YangHJ, et al. Humidifier disinfectant-associated children′s interstitial lung disease[J]. Am J Respir Crit Care Med, 2014,189(1):48-56. DOI: 10.1164/rccm.201306-1088OC.
[12]HongSB, KimHJ, HuhJW, et al. A cluster of lung injury associated with home humidifier use: clinical, radiological and pathological description of a new syndrome[J]. Thorax, 2014,69(8):694-702. DOI: 10.1136/thoraxjnl-2013-204135.
[13]PaekD, KohY, ParkDU, et al. Nationwide Study of Humidifier Disinfectant Lung Injury in South Korea, 1994-2011. Incidence and Dose-Response Relationships[J]. Ann Am Thorac Soc, 2015,12(12):1813-1821. DOI: 10.1513/AnnalsATS.201504-221OC.
[14]YoonJ, ChoHJ, LeeE, et al. Rate of humidifier and humidifier disinfectant usage in Korean children: A nationwide epidemiologic study[J]. Environ Res, 2017,155:60-63. DOI: 10.1016/j.envres.2017.01.030.
[15]ParkD, LeemJ, LeeK, et al. Exposure characteristics of familial cases of lung injury associated with the use of humidifier disinfectants[J]. Environ Health, 2014,13:70. DOI: 10.1186/1476-069X-13-70.
[16]ParkDU, RyuSH, LimHK, et al. Types of household humidifier disinfectant and associated risk of lung injury (HDLI) in South Korea[J]. Sci Total Environ, 2017,596-597: 53-60. DOI: 10.1016/j.scitotenv.2017.04.040.
[17]ParkD. Major concerns regarding lung injury and related health conditions caused by the use of humidifier disinfectant[J]. Environ Health Toxicol, 2016,31:e2016014. DOI: 10.5620/eht.e2016014.
[18]JeonBH, ParkYJ. Frequency of humidifier and humidifier disinfectant usage in gyeonggi provine[J]. Environ Health Toxicol, 2012,27:e2012002. DOI: 10.5620/eht.2012.27.e2012002.
[19]ParkJH, KimHJ, KwonGY, et al. Humidifier Disinfectants Are a Cause of Lung Injury among Adults in South Korea: A Community-Based Case-Control Study[J]. PLoS One, 2016,11(3):e0151849. DOI: 10.1371/journal.pone.0151849.
[20]ChangMH, ParkH, HaM, et al. Characteristics of Humidifier Use in Korean Pregnant Women: The Mothers and Children′s Environmental Health (MOCEH) Study[J]. Environ Health Toxicol, 2012,27:e2012003. DOI: 10.5620/eht.2012.27.e2012003.
[21]ParkDU, FriesenMC, RohHS, et al. Estimating retrospective exposure of household humidifier disinfectants[J]. Indoor Air, 2015,25(6):631-640. DOI: 10.1111/ina.12180.
[22]ParkDU, RyuSH, RohHS, et al. Association of high-level humidifier disinfectant exposure with lung injury in preschool children[J]. Sci Total Environ, 2018,616-617:855-862. DOI: 10.1016/j.scitotenv.2017.10.237.
[23]ParkS, LeeK, LeeEJ, et al. Humidifier disinfectant-associated interstitial lung disease in an animal model induced by polyhexamethylene guanidine aerosol[J]. Am J Respir Crit Care Med, 2014,190(6):706-708. DOI: 10.1164/rccm.201404-0710LE.
[24]SongJA, ParkHJ, YangMJ, et al. Polyhexamethyleneguanidine phosphate induces severe lung inflammation, fibrosis, and thymic atrophy[J]. Food Chem Toxicol, 2014,69:267-275. DOI: 10.1016/j.fct.2014.04.027.
[25]SongJ, KimW, KimYB, et al. Time course of polyhexamethyleneguanidine phosphate-induced lung inflammation and fibrosis in mice[J]. Toxicol Appl Pharmacol, 2018,345:94-102. DOI: 10.1016/j.taap.2018.02.013.
[26]ShimHE, LeeJY, LeeCH, et al. Quantification of inhaled aerosol particles composed of toxic household disinfectant using radioanalytical method[J]. Chemosphere, 2018,207:649-654. DOI: 10.1016/j.chemosphere.2018.05.132.
[27]祝肖肖,孟涛,冷曙光,等.重复吸入阳离子胍类消毒剂引起小鼠肺的纤维化改变研究[J].中华预防医学杂志, 2020, 54(2):198-202. DOI: 10.3760/cma.j.issn.0253-9624.2020.02.016.
[28]KimHY, KimMS, KimSH, et al. Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice[J]. Molecules, 2018,23(8). DOI: 10.3390/molecules23081974.
[29]KimMS, HanJY, KimSH, et al. Oleanolic acid acetate attenuates polyhexamethylene guanidine phosphate-induced pulmonary inflammation and fibrosis in mice[J]. Respir Physiol Neurobiol, 2018,252-253:1-9. DOI: 10.1016/j.resp.2018.03.001.
[30]KimMS, KimSH, JeonD, et al. Low-dose cadmium exposure exacerbates polyhexamethylene guanidine-induced lung fibrosis in mice[J]. J Toxicol Environ Health A, 2018,81(11):384-396. DOI: 10.1080/15287394.2018.1451177.
[31]KimMS, KimSH, JeonD, et al. Changes in expression of cytokines in polyhexamethylene guanidine-induced lung fibrosis in mice: Comparison of bleomycin-induced lung fibrosis[J]. Toxicology, 2018,393:185-192. DOI: 10.1016/j.tox.2017.11.017.
[32]KimHR, ShinDY, ChungKH. The role of NF-κB signaling pathway in polyhexamethylene guanidine phosphate induced inflammatory response in mouse macrophage RAW264.7 cells[J]. Toxicol Lett, 2015,233(2):148-155. DOI: 10.1016/j.toxlet.2015.01.005.
[33]KimMS, HanJY, KimSH, et al. Polyhexamethylene guanidine phosphate induces IL-6 and TNF-α expression through JNK-dependent pathway in human lung epithelial cells[J].J Toxicol Sci,2018,43(8):485-492. DOI: 10.2131/jts.43.485.
[34]JungHN, ZerinT, PodderB, et al. Cytotoxicity and gene expression profiling of polyhexamethylene guanidine hydrochloride in human alveolar A549 cells[J]. Toxicol In Vitro, 2014,28(4):684-692. DOI: 10.1016/j.tiv.2014.02.004.
[35]KimHR, ShinDY, ChungKH. A review of current studies on cellular and molecular mechanisms underlying pulmonary fibrosis induced by chemicals[J]. Environ Health Toxicol, 2018,33(3):e2018014-2018010. DOI: 10.5620/eht.e2018014.
[36]ShinDY, JeongMH, BangIJ, et al. MicroRNA regulatory networks reflective of polyhexamethylene guanidine phosphate-induced fibrosis in A549 human alveolar adenocarcinoma cells[J]. Toxicol Lett, 2018,287:49-58. DOI: 10.1016/j.toxlet.2018.01.010.

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