天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (9): 917-923.doi: 10.11958/20190637

• 实验研究 • 上一篇    下一篇

等毒性剂量芥子气不同途径诱导大鼠急性肺损伤的氧化应激反应差异探讨

胡晓璇 1，于丹 2，谢剑炜 2，许德凤 3△，钟玉绪 2△   

  1. 基金项目：全军后勤科研重大项目（AWS11C004） 作者单位：1宁夏医科大学上海市浦东新区公利医院培养基地（邮编200135）；2军事医学研究院毒物药物研究所，毒理学与抗毒药物国家 重点实验室；3上海市浦东新区公利医院呼吸内科 作者简介：胡晓璇（1993），女，硕士在读，主要从事急性肺损伤毒理机制方面研究 △通讯作者 许德凤 E-mail: xdfm2016@163.com；钟玉绪 E-mail: yuxuzhong2008@163.com
  • 收稿日期:2019-03-08 修回日期:2019-08-03 出版日期:2019-09-15 发布日期:2019-09-18
  • 通讯作者: 胡晓璇 E-mail:hxxdr6927@163.com
  • 基金资助:
    全军后勤科研重大项目

Differential oxidative stress reactions in sulfur mustard-induced acute pulmonary injury with equal toxicity dose in rats via different routes

HU Xiao-xuan1, YU Dan2, XIE Jian-wei2, XU De-feng3△, ZHONG Yu-xu2△   

  1. 1 Ningxia Medical University Shanghai Gongli Hospital Postgraduate Training Base, Shanghai 200135, China; 2 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology； 3 Department of Respiratory, Shanghai Gongli Hospital
  • Received:2019-03-08 Revised:2019-08-03 Published:2019-09-15 Online:2019-09-18
  • Contact: Xiao-Xuan HU E-mail:hxxdr6927@163.com

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摘要： 目的 通过建立大鼠经腹腔和气管途径等毒性剂量（1LD50）芥子气（SM）急性肺损伤模型，比较2种肺损伤 模型氧化应激反应的差异性。方法 选取Sprague Dawley大鼠，随机分为腹腔SM组，腹腔丙二醇组，气管SM组，气 管丙二醇组，正常组。采用酶联免疫吸附法和免疫组化法，检测血清酶和肺泡间隔相关蛋白表达。结果 大鼠腹腔 SM组血清各时间点超过氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）水平均高于同时 点气管SM组（P＜0.05）；腹腔SM组肺泡间隔各时间点铜锌超过氧化物歧化酶（CuZn-SOD）、锰超过氧化物歧化酶 （Mn-SOD）、对氧磷酶-1（PON-1）、载脂蛋白-1（ApoA1）表达的阳性细胞亦均高于气管SM组（P＜0.05)。结论 暴露 SM（1LD50）后，2种大鼠急性肺损伤模型在分子水平氧化应激反应存在着差异性，提示等毒性剂量SM所致大鼠的氧 化应激反应与染毒途径相关，并为抗氧化剂的应用提供了重要的理论依据。

关键词: 急性肺损伤, 芥子气, 氧化性应激, 疾病模型, 动物, 等毒性剂量

Abstract: Objective To compare oxidative stress responses of two acute pulmonary injury models induced by a toxicity dose (1LD50) of mustard gas (SM) in rats through intraperitoneal and tracheal pathways. Methods Male Sprague Dawley rats were selected and randomly divided into the intraperitoneal SM group, the intraperitoneal propylene glycol group, the tracheal SM group, the tracheal propylene glycol group and normal group. The serum enzyme levels and proteins related expressions in alveolar septum were measured by ELISA and immunohistochemistry methods. Results Serum levels of superoxide dismutase, catalase and glutathion peroxidase at different time points were increased in the intraperitoneal SM group compared with those of tracheal SM group (P＜0.05). In the alveolar septum, the positive cells of CuZn-superoxide dismutase, Mn-superoxide dismutase, paraoxonase-1 and apolipoprotein-1 expression were increased in the intraperitoneal SM group compared with those of tracheal SM group (P＜0.05). Conclusion At a dose of SM (1LD50), there are differences in the oxidative stress responses at the molecular level in two rat models of acute pulmonary injury. The results suggest that the oxidative stress responses reduced by equal toxicity dose (1LD50) of SM in rats are related to the toxic pathway, and which provides an important theoretical basis for the application of antioxidants.

Key words: acute pulmonary injury, mustard gas, oxidative stress, disease models, animal, equal toxic dose