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

Abstract

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

CLC Number:

R827.12

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.

References

[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.

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

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