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浙江大学学报（医学版）
浙江大学学报（医学版）  2016, Vol. 45 Issue (5): 522-529    DOI: 10.3785/j.issn.1008-9292.2016.09.11
原著     
不同模式口鼻式吸烟诱导急性肺损伤的实验研究
肖卫强1, 周国俊1, 许成云2, 徐建1, 黄芳芳1, 卢昕博1, 李霞1, 吴希美2
1. 浙江中烟工业有限责任公司技术中心, 浙江 杭州 310024;
2. 浙江大学医学院药理学系, 浙江 杭州 310058
Cigarette smoking in different manners induces acute lung injury in rats
XIAO Weiqiang1, ZHOU Guojun1, XU Chengyun2, XU Jian1, HUANG Fangfang1, LU Xinbo1, LI Xia1, WU Ximei2
1. Technology Center, China Tobacco Zhejiang Industrial Co. Ltd, Hangzhou 310024, China;
2. Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, China
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摘要：

目的：研究不同抽吸模式的口鼻式吸烟方式诱导大鼠急性肺损伤的效应。方法：市售焦油含量分别为1、5、11 mg的卷烟按照加拿大深度抽吸模式（深度抽吸）及11 mg焦油含量的卷烟按国际标准抽吸模式（国标抽吸）抽吸，并以空气为载气将卷烟烟雾载入大鼠口鼻暴露塔中；大鼠固定于固定器中，仅口鼻暴露于主流烟气中，吸烟28 d后处死大鼠进行左肺肺泡灌洗，肺泡灌洗液用于炎症细胞计数和分类以及ELISA检测炎症因子IL-1β和TNF-α水平；右肺下叶进行组织病理学观察；右肺上叶冻存并用于髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）活性及还原型谷胱甘肽（GSH）、活性氧和丙二醛含量检测。结果：同等抽吸模式下，大鼠吸入卷烟的烟气质量浓度与样品卷烟盒标记的焦油等有害物质含量成正比。大鼠吸烟一周后即出现体质量下降。深度抽吸及国标抽吸11 mg焦油含量的卷烟均能显著诱导大鼠肺部巨噬细胞、淋巴细胞和中性粒细胞浸润，IL-1β和TNF-α分泌增加，以及MPO活性提高（均P<0.05）；反映肺组织氧化应激水平的GSH含量和SOD活性均显著下降（均P<0.05），活性氧和丙二醛含量则显著上升（均P<0.05）。深度抽吸5 mg焦油含量的卷烟能显著诱导淋巴细胞和中性粒细胞浸润、IL-1β和TNF-α分泌以及肺组织MPO活性上升，同时能显著促使肺组织中GSH含量及SOD活性下降以及活性氧和丙二醛含量增加（均P<0.05）；但深度抽吸1 mg焦油含量的卷烟无明显诱导炎症细胞浸润等作用。结论：口鼻式吸烟方式可以成功诱导大鼠肺损伤模型，大鼠肺部炎症细胞浸润程度、炎症因子分泌及氧化应激水平与主流烟气中有害物质含量成正比。
关键词： 吸烟/副作用;  肺/损伤;  烟草;  疾病模型;  动物    
Abstract:

Objective: To investigate the effects of cigarette smoking in different manners on acute lung injury in rats. Methods: The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking (health canada method, HCM) manner, and those with tar of 11 mg were also smoked in international standard (ISO) smoking manner. Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure. After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro-inflammatory cytokines IL-1β and TNF-α. The right lungs were subjected to histological examination and determination of myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and glutathione, reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Results: In both HCM and ISO manners, the degree of lung injury was closely related to the tar content of cigarettes, and significant decrease in the body weight of rats was observed after smoking for one week. In a HCM manner, smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages, lymphocytes and neutrophils into lungs, significant increase in IL-1β and TNF-α levels and MPO activities, and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels (all P<0.05). Smoking with cigarette of 5 mg tar led to moderate increase in IL-1β and TNF-α levels, and MPO activities (all P<0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels (all P<0.05). However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1β and TNF-α levels. Conclusion: Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes.
Key words: Smoking/adverse effects    Lung/injuries    Tobacco    Disease models, animal
收稿日期: 2015-09-15 出版日期: 2016-09-25
CLC:  R563  
基金资助:

浙江省重大科技专项计划（2013C03050）；国家重点基础研究发展计划（973计划）（2011CB944403）
通讯作者: 周国俊(1973-),男,博士;E-mail:zhougj@zjtobacco.com;http://orcid.org/0000-0002-7377-546X;吴希美(1970-)男,博士,教授;E-mail:xiwu@zju.edu.cn;http://orcid.org/0000-0002-3316-893X     E-mail: zhougj@zjtobacco.com;xiwu@zju.edu.cn
作者简介: 肖卫强(1984-),男,硕士,工程师,主要从事烟草化学和吸烟与健康研究;E-mail:xiaowq@zjtobacco.com;http://orcid.org/0000-0001-6187-5837
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引用本文:

肖卫强 等. 不同模式口鼻式吸烟诱导急性肺损伤的实验研究[J]. 浙江大学学报（医学版）, 2016, 45(5): 522-529.

XIAO Weiqiang, ZHOU Guojun, XU Chengyun, XU Jian, HUANG Fangfang, LU Xinbo, LI Xia, WU Ximei. Cigarette smoking in different manners induces acute lung injury in rats. Journal of ZheJiang University(Medical Science), 2016, 45(5): 522-529.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2016.09.11    或    http://www.zjujournals.com/med/CN/Y2016/V45/I5/522

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