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

doi:10.3969/j.issn.1004-616x.2025.01.002

癌变·畸变·突变 ›› 2025, Vol. 37 ›› Issue (1): 8-15.doi: 10.3969/j.issn.1004-616x.2025.01.002

• 论著 • 上一篇

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

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

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, 陕西省环境健康危害评估与防护重点实验室, 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:2024-10-23 修回日期:2024-12-26 发布日期:2025-01-25
通讯作者: 海春旭
作者简介:曹猛，E-mail：caomeng411@fmmu.edu.cn；并列第一作者,王振，E-mail：1292094019@qq.com。
基金资助:
医学人才助推项目(2022JBGS007)

Study on the protective effect of caffeic acid phenethyl ester against sulfur mustard-induced acute lung injury in mice

CAO Meng, WANG Zhen, GAO Tian, YU Weihua, LIU Jiangzheng, KONG Deqin, WU Hao, LONG Zi, WANG Zhao, LIU Rui, HAI Chunxu

Department of Military Toxicology and Chemical Defense Medicine of the School of Military Preventive Medicine, Air Force Medical University; Key Laboratory of Environmental Hazard Assessment and Prevention of Ministry of Education; Key Laboratory of Environmental Health Hazard Assessment and Protection of Shaanxi Province; Key Laboratory of Free Radical Biology and Medicine of Shaanxi Province, Xi'an 710032, Shaanxi, China

Received:2024-10-23 Revised:2024-12-26 Published:2025-01-25

摘要/Abstract

摘要： 目的：针对小鼠由糜烂性毒剂2-氯乙基乙基硫醚(CEES)暴露引起的急性肺损伤，研究咖啡酸苯乙酯(CAPE)的保护作用及相关机制。方法： 40只雄性C57BL/6小鼠，采用雾化吸入10%的CEES构建急性肺损伤模型，染毒1、25和49 h后分别给予CAPE(10 mg/kg)进行治疗。染毒后第3天检测小鼠肺功能指标呼吸时间(Ti)、吸气时间(Te)和松弛时间(Tr)和每分钟通气量(MVb)；然后处死小鼠，采集血清和肺组织，检测体质量和肺体比，HE染色后进行组织病理学检测；使用DHE荧光探针检测肺组织活性氧(ROS)水平；试剂盒检测丙二醛(MDA)含量、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)含量；RT-qPCR法检测肺组织抗氧化分子CAT、促炎分子TNF-α和IL-6的mRNA表达水平；ELISA试剂盒检测血清炎症因子TNF-α和IL-6含量。结果： CEES雾化吸入3 d后与CEES染毒组小鼠相比，CAPE治疗组小鼠肺功能指标Ti、Te、Tr和MVb显著恢复(均为P<0.05)，肺组织病理损伤程度减轻，同时肺组织ROS水平和MDA含量显著减少，伴有CAT和SOD含量增加(均为P<0.05)。此外，CAPE治疗组小鼠的肺组织及血清TNF-α和IL-6含量较CEES染毒组显著降低(均为P<0.05)。结论： CAPE通过抗炎抗氧化作用可有效缓解CEES诱导的小鼠急性肺损伤，可能是糜烂性毒剂的候选治疗药物。该研究为糜烂性毒剂中毒治疗的干预措施和潜在治疗药物研究奠定了基础。

关键词: 糜烂性毒剂, 咖啡酸苯乙酯, 炎症, 氧化应激, 急性肺损伤

Abstract: OBJECTIVE： To investigate the protective effects and underlying mechanisms of caffeic acid phenethyl ester (CAPE) against acute lung injury induced by exposure to the blister agent 2-chloroethyl ethyl sulfide (CEES) in mice. METHODS： Forty male C57BL/6 mice were exposed to 10% CEES via aerosol inhalation to induce an acute lung injury model. The mice were treated with CAPE (10 mg/kg) at 1，25，and 49 hours post-exposure. Respiratory time (Ti)，expiratory time (Te)，relaxation time (Tr)，and minute ventilation (MVb) were measured on the third day post-exposure as indicators of lung function. Subsequently，the mice were euthanized，and serum and lung tissues were collected to assess body mass and lung-to-body weight ratio. Histopathological examination was performed after hematoxylin and eosin (HE) staining. Reactive oxygen species (ROS) levels in lung tissues were detected using a DHE fluorescent probe. Malondialdehyde (MDA) content，catalase (CAT) activity，and superoxide dismutase (SOD) activity were measured using commercial kits. The mRNA expression levels of antioxidant molecule CAT and inflammatory molecules TNF-α and IL-6 in lung tissues were determined by RT-qPCR. The concentrations of serum inflammatory cytokines TNF-α and IL-6 were measured using ELISA kits. RESULTS： Compared with mice in the CEES-exposed group，mice in the CAPE-treated group exhibited significant recovery in lung function indices，including Ti，Te，Tr，and MVb (all P<0.05)，after 3 days of CEES aerosol inhalation. The degree of pathological damage in lung tissues was reduced. Concurrently，the levels of ROS and MDA in the lung tissue were significantly decreased，accompanied by increased levels of CAT and SOD (all P<0.05). Furthermore，the concentrations of TNF-α and IL-6 in both the lung tissue and serum in the CAPE-treated group were significantly lower than those in the CEES-exposed group (all P<0.05). CONCLUSION： CAPE effectively alleviated CEES-induced acute lung injury in mice through its anti-inflammatory and antioxidant properties，suggesting its potential as a therapeutic candidate for vesicant agent poisoning. This study provides a foundation for the investigation of interventional measures and potential therapeutic drugs for the treatment of vesicant agent poisoning.

Key words: blister agent, caffeic acid phenethyl ester, inflammation, oxidative stress, acute lung injury

中图分类号:

R827.12

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.

CAO Meng, WANG Zhen, GAO Tian, YU Weihua, LIU Jiangzheng, KONG Deqin, WU Hao, LONG Zi, WANG Zhao, LIU Rui, HAI Chunxu. Study on the protective effect of caffeic acid phenethyl ester against sulfur mustard-induced acute lung injury in mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(1): 8-15.

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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

Study on the protective effect of caffeic acid phenethyl ester against sulfur mustard-induced acute lung injury in mice

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