雾化吸入糜烂性毒剂2-氯乙基乙基硫醚对小鼠肺功能的影响

doi:10.3969/j.issn.1004-616x.2025.01.005

癌变·畸变·突变 ›› 2025, Vol. 37 ›› Issue (1): 27-32,38.doi: 10.3969/j.issn.1004-616x.2025.01.005

• 论著 • 上一篇

雾化吸入糜烂性毒剂2-氯乙基乙基硫醚对小鼠肺功能的影响

师敏婕^1,2, 李佳威², 郭晓洁^1,2, 王常艳^1,2, 樊振鹏², 刘江正², 李文丽², 孔德钦², 辛宝¹

1. 陕西中医药大学公共卫生学院, 陕西西安 712046;
2. 空军军医大学军事预防医学系军事毒理学与防化医学教研室, 特殊作业环境危害评估与防治教育部重点实验室, 陕西省自由基生物学与医学重点实验室, 陕西西安 710032

收稿日期:2024-06-17 修回日期:2024-10-17 发布日期:2025-01-25
通讯作者: 孔德钦, 辛宝
作者简介:师敏婕，E-mail：419162645@qq.com。
基金资助:
国家自然科学基金(32100996)；陕西省重点研发计划（2023-YBSF-297）

Effect of aerosol inhalation of a blister agent 2-chloroethyl ethyl sulfide on pulmonary function in mice

SHI Minjie^1,2, LI Jiawei², GUO Xiaojie^1,2, WANG Changyan^1,2, FAN Zhenpeng², LIU Jiangzheng², LI Wenli², KONG Deqin², XIN Bao¹

1. School of Public Health, Shaanxi University of Chinese Medicine, Xi'an 712046;
2. Department of Military Toxicology and Chemical Defense Medicine, School of Military Preventive Medicine, Air Force Medical University, Key Laboratory of Environmental Hazard Assessment and Prevention of Special Operations of Ministry of Education, Key Laboratory of Free Radical Biology and Medicine of Shaanxi Province, Xi'an 710032, Shaanxi, China

Received:2024-06-17 Revised:2024-10-17 Published:2025-01-25

摘要/Abstract

摘要： 目的：采用全身体积描记检测系统(WBP)检测雾化吸入糜烂性毒剂2-氯乙基乙基硫醚(CEES)对小鼠肺功能的影响，为糜烂性毒剂导致肺损伤的病因诊断提供参考依据。方法：将C57BL/6雄性小鼠随机分为对照组和CEES染毒组，CEES染毒组给予8% CEES雾化吸入，对照组雾化吸入等量无水乙醇溶剂，监测小鼠日常活动情况，检测72 h后小鼠体质量变化。应用WBP无创性检测肺功能各项指标差异，包括一般指标、潮气量、传导性指标、气道阻力指标、通气指标及每分钟通气量；采用HE染色检测肺组织病理学变化。结果：与对照组小鼠相比，CEES染毒组小鼠活动减少，体质量显著下降(P<0.05)；呼气峰值时间比率、最大吸气流速、呼吸频率指数、每分钟通气量降低(P<0.01)，吸气时间、呼气时间、吸气末端暂停时间、呼气末暂停比、气道狭窄指数、呼吸暂停次数升高(P<0.01)；HE染色结果显示CEES染毒组小鼠肺泡结构被压缩、肺间隔增厚、肺组织发生炎细胞浸润、肺泡内红细胞渗出。结论： CEES吸入后可导致小鼠吸气性和呼气性双向阻力增加，换气时间间隔延长，呼吸频率降低，引起肺通气不足。这些肺功能特点对糜烂性毒剂导致的肺损伤具有辅助诊断价值。

关键词: 糜烂性毒剂, 全身体积描记法, 肺功能, 急性肺损伤, 2-氯乙基乙基硫醚

Abstract: OBJECTIVE： The aims were to study effect of an inhalation blister agent，2-chloroethyl ethyl sulfide (CEES)，on the pulmonary function of mice by the whole body plethysmography (WBP) technology，and to provide an etiological evaluation of lung injury caused by the agent. METHODS： Male C57BL/6 mice were randomly divided into control and CEES exposure groups. The exposure group was given an aerosolized 8% CEES solution，while the control group was expose to an equal dose of solvent ethanol. The daily activity of the mice was monitored，and after 72 hours，the body weights were recorded. WBP was applied to non-invasively detect differences in various lung function characteristics，general indicators，tidal volume，conductivity indicators，airway resistance indicators，ventilation indicators，and minute ventilation. Hematoxylin-eosin (HE) staining was used to detect pathological changes in lung tissue. RESULTS： Compared with control mice，the CEES-exposed group showed reduced activity and a significant decrease in body weight；rate of achieving peak expiratory flow，peak-inspiratory-flow，frequency，and minute volume decreased (P<0.01)；inspiration time，expiration-time，end-inspiratory-pause，time of pause at end of expiration，pause enhanced，and pause increased (P<0.01)；compressed lung alveolar structures，thickened lung septa，infiltration of inflammatory cells in the lung tissue，and entrance of red blood cells into the alveoli. CONCLUSION： Inhalation of blister agents led to increased inspiratory and expiratory bidirectional resistance，prolonged ventilation intervals，decreased respiratory rate，and pulmonary hypoventilation. These may be characteristics of blister agent-induced lung injury.

Key words: blister agents, whole body plethsmography, pulmonary function, acute lung injury, CEES

中图分类号:

R827.12

师敏婕, 李佳威, 郭晓洁, 王常艳, 樊振鹏, 刘江正, 李文丽, 孔德钦, 辛宝. 雾化吸入糜烂性毒剂2-氯乙基乙基硫醚对小鼠肺功能的影响[J]. 癌变·畸变·突变, 2025, 37(1): 27-32,38.

SHI Minjie, LI Jiawei, GUO Xiaojie, WANG Changyan, FAN Zhenpeng, LIU Jiangzheng, LI Wenli, KONG Deqin, XIN Bao. Effect of aerosol inhalation of a blister agent 2-chloroethyl ethyl sulfide on pulmonary function in mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(1): 27-32,38.

参考文献

[1] RAFATI-RAHIMZADEH M, RAFATI-RAHIMZADEH M, KAZEMI S, et al. Therapeutic options to treat mustard gas poisoning-review[J]. Caspian J Intern Med, 2019, 10(3): 241-264.
[2] RAFATI-RAHIMZADEH M, RAFATI-RAHIMZADEH M, KAZEMI S, et al. Ophthalmological aspects of mustard gas poisoning (focus on management)[J]. Caspian J Intern Med, 2022, 13(3): 458-468.
[3] KAVOUSI S, AKBARIALIABAD H, MEHRABANI D, et al. The predictive association between radiological findings and lung cancer development in patients exposed to sulfur mustard gas: 4 decades follow up of 719 victims[J]. BMC Pulm Med, 2022, 22(1): 481.
[4] MAO G C, GONG C C, WANG Z, et al. BMSC-derived exosomes ameliorate sulfur mustard-induced acute lung injury by regulating the GPRC5A-YAP axis[J]. Acta Pharmacol Sin, 2021, 42(12): 2082-2093.
[5] KHAZDAIR M R, BOSKABADY M H. Possible treatment with medicinal herbs and their ingredients of lung disorders induced by sulfur mustard exposures: a review[J]. Environ Sci Pollut Res Int, 2021, 28(39): 54191-54208.
[6] STANOJEVIC S, KAMINSKY D A, MILLER M R, et al. ERS/ATS technical standard on interpretive strategies for routine lung function tests[J]. Eur Respir J, 2022, 60(1): 2101499.
[7] 李树民, 张敏, 王朋, 等. 小鼠无创性肺功能的测定及其意义[J]. 中国实验动物学报, 2018, 26(5): 548-553.
[8] MIRSHARIF E S, SHAMS J, FALAHI F, et al. Peripheral blood mononuclear cellular viability and its correlation with long-term pulmonary complications after sulfur mustard exposure[J]. Int Immunopharmacol, 2019, 76: 105814.
[9] MAJD A M M, FAGHIHZADEH S, POURFARZAM S, et al. Serum and sputum levels of IL-17, IL-21, TNFα and mRNA expression of IL-17 in sulfur mustard lung tissue with long term pulmonary complications (28 years after sulfur mustard exposure)[J]. Int Immunopharmacol, 2019, 76: 105828.
[10] KHAZDAIR M R, GHORANI V, ALAVINEZHAD A, et al. Effect of Zataria multiflora on serum cytokine levels and pulmonary function tests in sulfur mustard-induced lung disorders: a randomized double-blind clinical trial[J]. J Ethnopharmacol, 2020, 248: 112325.
[11] MORADI F, KJELLBERG S, LI Y, et al. Respiratory function after 30+ years following sulfur mustard exposure in survivors in Sweden[J]. Front Med, 2024, 11: 1251500.
[12] SUNIL V R, PATEL-VAYAS K, SHEN J L, et al. Role of TNFR1 in lung injury and altered lung function induced by the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide[J]. Toxicol Appl Pharmacol, 2011, 250(3): 245-255.
[13] O’NEILL H C, WHITE C W, VERESS L A, et al. Treatment with the catalytic metalloporphyrin AEOL 10150 reduces inflammation and oxidative stress due to inhalation of the sulfur mustard analog 2-chloroethyl ethyl sulfide[J]. Free Radic Biol Med, 2010, 48(9): 1188-1196.
[14] SADEGHI S, TAPAK M, GHAZANFARI T, et al. A review of sulfur mustard-induced pulmonary immunopathology: an alveolar macrophage approach[J]. Toxicol Lett, 2020, 333: 115-129.
[15] MALAVIYA R, LASKIN J D, LASKIN D L. Long-term respiratory effects of mustard vesicants[J]. Toxicol Lett, 2020, 319: 168-174.
[16] 周俊雅, 冯丽丽, 刘锦凯. 肺功能检查时预防新冠感染的措施及效果[J]. 工业卫生与职业病, 2023, 49(4): 382-383.
[17] 孟燊, 叶盛, 杨晋, 等. 肺功能检查在慢性阻塞性肺疾病诊断中的应用进展[J]. 山东医药, 2023, 63(34): 111-115.
[18] JOST P, MUCKOVA L, PEJCHAL J. in vitro stress response induced by sulfur mustard in lung fibroblasts NHLF and human pulmonary epithelial cells A-549[J]. Arch Toxicol, 2020, 94(10): 3503-3514.
[19] BROMBERG L, CREASY W R, MCGARVEY D J, et al. Nucleophilic polymers and gels in hydrolytic degradation of chemical warfare agents[J]. ACS Appl Mater Interfaces, 2015, 7(39): 22001-22011.
[20] 欧阳雪莉. 孟鲁司特钠片联合布地奈德福莫特罗吸入粉雾剂(Ⅱ)治疗支气管哮喘的临床效果[J]. 临床合理用药, 2024, 17(17): 64-67.
[21] 高晶晶, 罗勇, 黄煜, 等. 慢性阻塞性肺疾病患者呼吸音声谱特征研究[J]. 声学技术, 2022, 41(4): 551-555.
[22] MEHRA R. Sleep apnea and the heart[J]. Cleve Clin J Med, 2019, 86(9 Suppl 1): 10-18.
[23] 马菁茹, 黄晶晶, 肖宽林. 儿童阻塞性睡眠呼吸暂停低通气综合征与常见炎症因子及相关疾病的关系[J]. 中国眼耳鼻喉科杂志, 2017, 17(5): 366-369.
[24] 徐俪颖, 赵玮, 王媛, 等. 穿山龙对支气管哮喘小鼠气道重构和上皮-间质转化的干预作用[J]. 中华中医药杂志, 2022, 37(12): 7007-7011.
[25] 尹健彬, 皮娜, 文怡, 等. 肺纤维化小鼠肺功能的动态变化[J]. 医学研究生学报, 2019, 32(12): 1237-1242.
[26] CONDOR CAPCHA J M, KAMIAR A, ROBLETO E, et al. Growth hormone-releasing hormone receptor antagonist MIA-602 attenuates cardiopulmonary injury induced by BSL-2 rVSV-SARS-CoV-2 in hACE2 mice[J]. Proc Natl Acad Sci U S A, 2023, 120(48): e2308342120.
[27] DAI Y X, DUAN K, HUANG G Y, et al. Inhalation of electronic cigarettes slightly affects lung function and inflammation in mice[J]. Front Toxicol, 2023, 5: 1232040.
[28] 孔汴躲. 布地奈德联合异丙托溴铵雾化吸入对阻塞性肺气肿患者肺功能的影响[J]. 北方药学, 2019, 16(5): 105-106.
[29] 靳小利. 布地奈德联合异丙托溴铵对阻塞性肺气肿患者气血参数及肺功能的影响[J]. 实用医技杂志, 2019, 26(3): 336-337.
[30] 强音, 蔡永桥, 杭晶卿, 等. 慢性气道疾病稳定期吸入药物能力与肺功能相关性[J]. 临床肺科杂志, 2022, 27(10): 1505-1508.
[31] 王金霞, 王玉玲, 王蓓, 等. 呼吸康复阀在慢阻肺气道黏液高分泌表型中的疗效观察[J]. 宁夏医学杂志, 2024, 46(5): 378-382.
[32] KHAZDAIR M R, BOSKABADY M H. Possible treatment approaches of sulfur mustard-induced lung disorders, experimental and clinical evidence, an updated review[J]. Front Med, 2022, 9: 791914.

雾化吸入糜烂性毒剂2-氯乙基乙基硫醚对小鼠肺功能的影响

Effect of aerosol inhalation of a blister agent 2-chloroethyl ethyl sulfide on pulmonary function in mice

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 13

编辑推荐

Metrics

本文评价

[1]	曹猛, 王振, 高天, 于卫华, 刘江正, 孔德钦, 吴昊, 龙子, 王钊, 刘瑞, 海春旭. 咖啡酸苯乙酯对硫芥诱导小鼠急性肺损伤的保护作用研究[J]. 癌变·畸变·突变, 2025, 37(1): 8-15.
[2]	师敏婕, 李嘉, 邓紫丰, 詹天豪, 刘建豪, 赵昱舜, 李文丽, 刘江正, 孔德钦. 盐酸右美托咪定对2-氯乙基乙基硫醚致人支气管上皮细胞损伤的保护作用及机制[J]. 癌变·畸变·突变, 2024, 36(5): 342-348,358.
[3]	孔德钦, 刘思佳, 刘建豪, 马耀, 马丞飞, 赵昱舜, 周嘉恒, 师敏婕, 李嘉, 刘江正. 肝细胞核因子-1b在糜烂性毒剂2-氯乙基乙基硫醚诱导急性肺支气管上皮细胞损伤中的作用及其机制[J]. 癌变·畸变·突变, 2024, 36(1): 1-8.
[4]	郭晓洁, 刘鹏晖, 龙子, 李佳威, 涂永梅, 李文丽, 刘启玲. 氧化应激致自噬在光气诱导的急性肺损伤中的作用[J]. 癌变·畸变·突变, 2023, 35(5): 325-333,340.
[5]	王钊, 刘思佳, 刘建豪, 马丞飞, 赵昱舜, 徐安琦, 艾多, 戚羽佳, 孔德钦, 刘江正. 糜烂性毒剂氮芥染毒对肝细胞线粒体结构和功能的影响[J]. 癌变·畸变·突变, 2023, 35(2): 102-108,153.
[6]	于婧, 冯丹丹, 潘文森. 桑黄素在脂多糖诱导的急性肺损伤中的相关机制[J]. 癌变·畸变·突变, 2022, 34(3): 213-218.
[7]	陈东亚, 陆罗定, 陈耿, 张颖, 俞萍, 吕中明, 卞倩. 丹参酮ⅡA磺酸钠对环境细颗粒物诱导的大鼠肺部损伤的保护作用[J]. 癌变·畸变·突变, 2022, 34(1): 25-29,34.
[8]	陈文龙, 由淑萍, 赵军, 张杰, 刘涛. 阿尔泰金莲花浸膏粉对PM2.5致大鼠急性肺损伤的保护作用[J]. 癌变·畸变·突变, 2019, 31(1): 22-28.
[9]	刘萌萌, 李彦文, 周庆彪, 张佳欣, 王乐乐, 刘江正, 于卫华, 孔德钦, 刘瑞, 海春旭, 张晓迪. 氯气吸入致大鼠肺血管内皮细胞的线粒体损伤及红景天苷的干预作用[J]. 癌变·畸变·突变, 2018, 30(1): 31-36,41.
[10]	凌亚豪, 魏金锋, 王爱平, 靳洪涛. 急性肺损伤和急性呼吸窘迫综合征发病机制的研究进展[J]. 癌变·畸变·突变, 2017, 29(2): 151-154.
[11]	刘萌萌, 孔德钦, 邹远康, 王乐乐, 刘瑞, 海春旭, 张晓迪. 红景天苷对氯气暴露致急性肺损伤肺血管通透性的保护作用[J]. 癌变·畸变·突变, 2016, 28(5): 377-382.
[12]	龙子，孔德钦，海春旭，王欣. 光气中毒致肺泡上皮细胞线粒体结构和功能损伤的研究[J]. 癌变·畸变·突变, 2015, 27(1): 54-58.
[13]	杨东海;张涛;刘瑞;刘江正;秦绪军;王钊;张伟;柏桦;海春旭;陈宏莉2. 丙酮酸乙酯对氯气染毒大鼠肺氧化应激损伤的保护作用[J]. , 2012, 24(4): 253-255,.