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丙酮酸乙酯对氯气染毒大鼠肺组织炎症的抑制作用

 琰1,张 涛2,刘江正2,秦绪军2,王 钊2,海春旭2,陈宏莉2,*   

  1. ( 1. 第四军医大学西京医院门诊部特诊科,陕西 西安 710033;2. 第四军医大学军事预防医学院毒理学教研室,陕西 西安 710032 )
  • 收稿日期:2012-11-21 修回日期:2013-04-02 出版日期:2013-09-30 发布日期:2013-09-30
  • 通讯作者: 陈宏莉,Tel:029-84774882-802;E-mail:kaixing @ fmmu.edu.cn
  • 作者简介:程 琰 (1977- ),女,陕西省西安市人,研究方向:卫生毒理学。E-mail:chenfmmu@msn.com
  • 基金资助:

    国家自然科学基金资助 (30800903,30901172)

Ethyl pyruvate inhibits chlorine gas-induced lung inflammation

CHENG Yan1ZHANG Tao2,LIU Jiang-zheng2,QIN Xu-jun2,WANG Zhao2,HAI Chun-xu2,CHEN Hong-li2,*   

  1. (1. Outpatient Department, Xijing Hospital, Xi'an 710033; 2. Department of Toxicology, Fourth Military Medical University,  Xi'an 710032, Shaanxi, China)
  • Received:2012-11-21 Revised:2013-04-02 Online:2013-09-30 Published:2013-09-30
  • Contact: CHEN Hong-li,Tel:029-84774882-802;E-mail:kaixing @ fmmu.edu.cn

摘要:

 目的: 研究丙酮酸乙酯 (ethyl pyruvate,EP)对氯气导致的肺组织炎症反应的抑制作用及其机制。方法:60只SD雄性大鼠分为2批,每批随机分为阴性对照组、阳性对照组和EP处理组,每组各10只,阴性对照组以空气为对照。阳性对照组和EP处理组给予2 536 mg/m3的氯气动态染毒,染毒时间为20 min,染毒后立即分别腹腔注射生理盐水或EP (40 mg/kg)。染毒后6 h 采集肺泡灌洗液,检测TNF-α、IL-1β以及IL-8含量,取肺组织检测核因子NF-κB核转位。于染毒后24 h取肺组织检测高迁移率族蛋白B1(high mobility group box 1,HMGB1)的表达并检测ⅡA型分泌型磷脂酶A2 (type-ⅡA secretary phospholipase A2,sPLA2-ⅡA) 活性。结果:与阴性对照组比较,氯气染毒6 h后肺泡灌洗液中TNF-α、IL-1β、IL-8含量显著增加 (P<0.05),NF-κB核转位显著升高 (P<0.05),染毒后24 h肺组织中HMGB1表达以及sPLA2-ⅡA活性显著升高 (P<0.05)。与阳性对照组比较,给予EP处理后上述指标均显著降低 (P<0.05)。结论:氯气中毒后启动了早期和晚期炎症反应,引起肺组织释放大量炎症因子,导致炎症反应发生。EP处理可有效抑制肺组织炎症反应。

关键词:  氯气, 炎症反应, 丙酮酸乙酯, 肺组织

Abstract:

OBJECTIVE: To study the protective effect and mechanisms of ethyl pyruvate(EP) on pulmonary inflammation induced by chlorine gas. METHODSAdult male SD rats were exposed to chlorine gas of 2 536 mg/m3 or normal air for 20 min in a whole-body dynamic exposure chamber. EP (40 mg/kg) or vehicle(saline) was given by intraperitoneal injections immediately after chlorine gas exposure. Rats were killed at 6 hours and 24 hours after chlorine gas exposure. At 6 hours,levels of TNF-α,IL-1β and IL-8 in bronchoalveolar lavage fluid (BALF) and the nuclear translocation of nuclear factor κB (NF-κB) in the lung were evaluated. At 24 hours,the expression of HMGB1 and the activity of type-ⅡA secretary phospholipase A2 (sPLA2-ⅡA)were measured. RESULTSAt 6 hours after chlorine gas exposure,levels of TNF-α,IL-1β and IL-8 in BALF as well as NF-κB nuclear translocation increased significantly(P<0.05). Furthermore,at 24 hours,HMGB1 expression and sPLA2-ⅡA activity too were significantly increased(P<0.05). EP treatment attenuated these changes(P<0.05). CONCLUSION: Chlorine gas induced inflammation in the lung via activation of inflammatory mediators at early as well as late stage. EP treatment attenuated inflammation in the lung induced by chlorine gas.

Key words: chlorine gas, inflammation, ethyl pyruvate, lung tissue