大气细颗粒物致炎动物模型系统评价  

Systematic evaluation of pulmonary inflammation induced by fine particulate matter in a mouse model

作　　者：侯天芳 马元元[2] 王广发[1] HOU Tianfang;MA Yuanyuan;WANG Guangfa(Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing 100034, China;Department of Laboratory Animal Center, Peking University First Hospital, Beijing 100034)

机构地区：[1]北京大学第一医院呼吸和危重症科,北京100034 [2]北京大学第一医院实验动物中心,北京100034

出　　处：《中国实验动物学报》2018年第1期65-71,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金面上项目(No.81370106);首都卫生发展专项研究重点攻关项目(No.2016-1-4071);国家重点研发计划:慢病专项课题(No.2017YFC1309500);北京市自然科学基金重点项目(No.7161013);北京大学临床研究项目项目编号(PUCRP201303)~~

摘　　要：目的探索大气污染对动物的致病机制,对BALB/c小鼠采用无创性气管滴注PM2.5颗粒悬浮液的方法,构建大气污染致炎动物模型。方法将150只SPF级BALB/c小鼠随机分成空白对照组、生理盐水组、PM2.5低度组(2.5 mg/kg)、PM2.5中度组(5 mg/kg)和PM2.5高度组(10 mg/kg)共5组,各剂量组气管滴注第3天,第7天、第21天、第35天、第49天,气管滴注操作完成后24 h采取组织样本,采用ELISA、肺组织病理HE染色的方法,来验证无创性气管滴注方法的可行性和致炎模型构建成功与否。结果本建模方法,成功率高达96%。采用气管滴注法,建模小鼠肺组织炎症评分与气道滴注时间的延长和剂量呈正相关。PM2.5暴露后,肺内有大量淋巴细胞聚集及吞噬颗粒的巨噬细胞浸润,肺泡间隔增宽。各暴露组分别与生理盐水对照组、空白组比较,肺泡灌洗液中炎症因子IL-6、肺组织匀浆中TNF-α水平增高,高剂量组差异最显著。结论本实验用气管滴注法建立小鼠致炎模型成功,并证明此方法简单、可靠,可广泛用于小鼠呼吸系统重复滴注,有利于进一步研究大气污染及其他致炎机制。Objective The aim of this study was to establish a PM2. 5 air pollution-induced mouse model of pulmonary inflammation and investigate its pathogenetic mechanism. Methods 150 specific pathogen-free BALB/c mice were subjected to intratracheal instillation of 2. 5,5,or 10 mg/kg PM2. 5 suspension to construct airborne inflammation models.The blank group and saline group were taken as a control group. Mice were euthanized after 3rd,7th,21st,35th and 49th days to assess the pathological changes in lung tissues using HE staining and ELISA. Results The success rate of tracheal instillation was 96%. With the time prolongation and increasing doses of intratracheal PM2. 5 instillation,the histopathological scores of lung tissue increased gradually,showing alveolar macrophages with engulfed particles and lymphocyte accumulation in bronchiole and widened inter-alveolar space. The levels of BALF IL-6 and TNF-α of lung tissue homogenate were significantly increased in the high dose PM2. 5（ 10 mg/kg） group,compared with the control groups. Conclusions A mouse model of PM2. 5 air pollution-induced lung inflammation is successfully established by intratracheal instillation of PM2. 5 suspension. This method is proved to be simple,safe and reliable,and is useful for further study of air pollution-induced and other inflammatory mechanisms.

关 键 词：PM2.5 大气污染 气管滴注 模型 小鼠 

分 类 号：Q95-33[生物学—动物学]