催化性抗氧化剂AEOL-10150对氮芥诱导小鼠急性肝损伤的保护作用

doi:10.3969/j.issn.1004-616x.2022.01.008

癌变·畸变·突变 ›› 2022, Vol. 34 ›› Issue (1): 40-46,61.doi: 10.3969/j.issn.1004-616x.2022.01.008

催化性抗氧化剂AEOL-10150对氮芥诱导小鼠急性肝损伤的保护作用

艾多^1,2, 徐安琦^1,2, 孔德钦¹, 刘颖³, 于卫华¹, 王钊¹, 彭洁¹, 刘瑞¹, 张晓迪¹, 海春旭¹, 李文丽¹, 王欣¹, 刘江正¹

1. 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, 陕西省自由基生物学与医学重点实验室, 教育部特殊作业环境危害评估与防治重点实验室, 陕西西安 710032;
2. 空军军医大学基础医学院学员二大队, 陕西西安 710032;
3. 陆军防化学院, 北京 102205

收稿日期:2021-09-30 修回日期:2021-12-20 出版日期:2022-01-31 发布日期:2022-02-15
通讯作者: 刘江正,E-mail:liujiangzh@fmmu.edu.cn E-mail:liujiangzh@fmmu.edu.cn
作者简介:艾多,E-mail:553248978@qq.com
基金资助:
国家自然科学基金青年科学基金（31900892）

Protective effects of catalytic antioxidant AEOL-10150 against nitrogen mustard-induced acute liver injury in mice

AI Duo^1,2, XU Anqi^1,2, KONG Deqin¹, LIU Ying³, YU Weihua¹, WANG Zhao¹, PENG Jie¹, LIU Rui¹, ZHANG Xiaodi¹, HAI Chunxu¹, LI Wenli¹, WANG Xin¹, LIU Jiangzheng¹

1. Department of Military Toxicology and Chemical Defense Medicine, School of Military Preventive Medicine, Air Force Medical University, Key Laboratory of Free Radical Biology and Medicine of Shaanxi Province, Key Laboratory of Environmental Hazard Assessment and Prevention of Special Operations of Ministry of Education, Xi'an 710032, Shaanxi;
2. The Second Brigade of Basic Medical College, Air Force Medical University, Xi'an 710032, Shaanxi;
3. Institute of Nuclear, Biological and Chemical Defense, Beijing 102205, China

Received:2021-09-30 Revised:2021-12-20 Online:2022-01-31 Published:2022-02-15

摘要/Abstract

摘要： 目的： 探讨催化性抗氧化剂AEOL-10150对氮芥诱导小鼠肝损伤的保护作用及其机制。方法： 实验对象为C57BL/6小鼠，采用腹腔单次注射盐酸氮芥（2 mg/kg）构建急性肝损伤模型，染毒后0.5和6 h分别给予AEOL-10150（5 mg/kg）进行治疗干预，染毒3 d后处死小鼠，收集眼球血液和肝组织，观察肝组织大体改变和HE染色后进行组织病理学检测；检测血清谷丙转氨酶（ALT）和谷草转氨酶（AST）活性，肝组织活性氧（ROS）水平、丙二醛（MDA）含量和还原型谷胱甘肽（GSH）含量，肝组织氧化还原调控分子Nrf-2的mRNA表达水平，肝组织髓过氧化物酶（MPO）活性，血清炎症因子TNF-α、IL-1β含量。结果： 2 mg/kg的氮芥单次腹腔注射3 d后可以成功诱导小鼠肝组织氧化损伤和炎症反应。与氮芥染毒组小鼠相比，AEOL-10150治疗组动物肝组织病理损伤程度减轻，血清ALT和AST活性降低，同时肝组织ROS水平和MDA含量显著减少，伴有GSH含量增加和Nrf-2的mRNA和蛋白表达水平降低（均为P<0.05）。此外，AEOL-10150治疗组小鼠的肝组织MPO活性及血清TNF-α、IL-1β浓度较氮芥染毒组显著降低（均为P<0.05）。结论： AEOL-10150能够有效减轻氮芥诱导的小鼠急性肝损伤，其机制可能与直接抗氧化作用及抗炎效应有关。

关键词: AEOL-10150, 氮芥, 氧化应激, 炎症, 保护作用

Abstract: OBJECTIVE: To investigate protective effects of a catalytic antioxidant AEOL-10150 against nitrogen mustard-induced liver injury and related mechanisms. METHODS: A single intraperitoneal injection of nitrogen mustard hydrochloride (2 mg/kg) was used to construct a nitrogen mustard-induced acute liver injury model in C57BL/6 mice. AEOL-10150 (5 mg/kg) was given 0.5 and 6 h for treatment intervention after nitrogen mustard exposure,and sacrificed after 3 days of exposure. For clarifying the AEOL-10150 has a protective effect on nitrogen mustard-induced liver injury in mice,the following indicators were evaluated:gross liver tissue changes and pathological changes by HE stain;serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities;liver tissue reactive oxygen species (ROS) level,malondialdehyde (MDA) content;reduced glutathione (GSH) content;liver tissue redox regulatory molecule Nrf-2 mRNA and protein expression level;liver tissue myeloperoxidase (MPO) activity,and serum inflammatory factors TNF-α,IL-1β content. RESULTS: A single intraperitoneal exposure of 2 mg/kg nitrogen mustard successfully induced oxidative damage and inflammatory response in livers of mice in the 3rd day. Compared with nitrogen mustard-exposed mice,the AEOL-10150 intervention reduced liver tissue pathological damage,decreased serum ALT and AST activities,and significantly reduced liver tissue ROS and MDA levels,accompanied by the increased GSH content and the decreased Nrf-2 level. In addition,the liver tissue MPO activities and serum TNF-α and IL-1β concentrations of mice in the AEOL-10150 intervention group were significantly lower than those in the nitrogen mustard-exposed group. CONCLUSION: AEOL-10150 effectively alleviated the acute liver injuries which were induced by nitrogen mustard in mice,and its mechanism might be related to direct antioxidant effect and anti-inflammatory effect.

Key words: AEOL-10150, nitrogen mustard, oxidative stress, inflammation, protective effect

中图分类号:

R827.15

艾多, 徐安琦, 孔德钦, 刘颖, 于卫华, 王钊, 彭洁, 刘瑞, 张晓迪, 海春旭, 李文丽, 王欣, 刘江正. 催化性抗氧化剂AEOL-10150对氮芥诱导小鼠急性肝损伤的保护作用[J]. 癌变·畸变·突变, 2022, 34(1): 40-46,61.

AI Duo, XU Anqi, KONG Deqin, LIU Ying, YU Weihua, WANG Zhao, PENG Jie, LIU Rui, ZHANG Xiaodi, HAI Chunxu, LI Wenli, WANG Xin, LIU Jiangzheng. Protective effects of catalytic antioxidant AEOL-10150 against nitrogen mustard-induced acute liver injury in mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(1): 40-46,61.

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催化性抗氧化剂AEOL-10150对氮芥诱导小鼠急性肝损伤的保护作用

Protective effects of catalytic antioxidant AEOL-10150 against nitrogen mustard-induced acute liver injury in mice

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