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芥子气中毒机制及防护药物研究进展
杨玉彦,高焕焕,孙铭学,孟文琪,赵杰,肖凯*
0
(第二军医大学热带医学与公共卫生学系防化医学教研室, 上海 200433
*通信作者)
摘要:
芥子气(SM)是一种双功能烃化剂,能与蛋白质、DNA、RNA等多种生物大分子发生烃化反应,其中与DNA发生反应是其最重要的毒理机制之一。SM损伤机制主要包括DNA损伤、多聚腺苷二磷酸核糖聚合酶(PARP)激活、氧化应激、炎症及免疫调节反应和蛋白水解酶激活等。目前临床上尚无SM特效药物,主要是对症治疗。目前对症治疗SM使用的主要药物有自由基清除剂及抗氧化剂、PARP抑制剂、抗炎药物及蛋白酶抑制剂等。本文总结了SM的毒理机制及相应的防护药物研究进展。
关键词:  芥子气  中毒机制  预防和防护用药
DOI:10.16781/j.0258-879x.2016.09.1121
投稿时间:2016-05-11修订日期:2016-08-26
基金项目:国家科技新药创制重大专项(2013ZX09J13103-02C),全军后勤科研项目重大子项(AWS11C004重大子项-08),上海市卫生和计划生育委员会公共卫生建设三年行动计划,上海市卫生计生系统核生化支撑项目.
Poisoning mechanism and protective drugs of sulfur mustard: an update
YANG Yu-yan,GAO Huan-huan,SUN Ming-xue,MENG Wen-qi,ZHAO Jie,XIAO Kai*
(Department of Chemical Defense Medicine, Faculty of Tropical Medicine and Public Health, Second Military Medical University, Shanghai 200433, China
*Corresponding author)
Abstract:
Sulfur mustard (SM) is a bifunctional alkylating agent that can react with multiple biochemical molecules such as DNA, RNA, proteins, and so on, and its alkylation with DNA is one of the major poisoning mechanisms. Presently the pathogenesis of SM included DNA alkylation, poly ADP-ribose polymerase (PARP) activation, oxidative stress, inflammation, activation of immunoregulation and proteolytic enzymes, etc. By now there have been no specific antidotes in clinical treatment, and all the existing drugs are mainly used for symptomatic treatment. The drugs used clinically and currently being under development include free radical scavengers, antioxidant agents, PARP inhibitors, anti-inflammatory drugs and protease inhibitors. This review summarized the advances in pathogenesis of SM and the corresponding protective drugs.
Key words:  mustard gas  toxicity mechanism  protective agents