氮杂纳米二氧化钛对肺的损伤效应  

Pulmonary injury induced by nitrogen-doped nano titanium dioxide

作　　者：于彩霞 陈维艳 龙琦 禚昌龙 曹文斌[3] 刘文秀[3] 卢怡[4] 李蓉 周紫垣 张爱华 YU Cai-xia;CHEN Wei- yan;LONG Qi;ZHUO Chang-long;CAO Wen-bin;LIU Wen-xiu;LU Yi;LI Rong;ZHOU Zi-yuan;ZHANG Ai-hua(School of Public Health, Guizhou Medical University, Guiyang, Guizhou 550025, China;Department of Environmental Health, College of Military Preventive Medicine, Army Medical University, Chongqing 400038, China;School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China;The 306th Hospital of PLA, Beijing 100101, China;77120 Troop Health Company of PLA, Chengdu, Sichuan 610081, China)

机构地区：[1]贵州医科大学公共卫生学院毒理卫生教研室,贵州贵阳550025 [2]陆军军医大学军事预防医学院环境卫生教研室,重庆400038 [3]北京科技大学材料科学与工程学院,北京100083 [4]中国人民解放军第306医院,北京100101 [5]四川成都市金牛区凤凰山77120部队卫生连,四川成都610081

出　　处：《环境与职业医学》2018年第4期291-296,共6页Journal of Environmental and Occupational Medicine

基　　金：军队后勤科研重点项目(编号：BZZ14J001);军队后勤科研重大项目(编号：ASW13J002);国家重点研发计划(编号：2016YFC0700901);北京市科技计划(编号：Z151100003915091)

摘　　要：[目的]探究新型纳米材料氮杂纳米二氧化钛(N-nTiO_2)对肺的损伤效应。[方法]42只健康SPF级SD大鼠随机分为1个空白对照组和5个N-nTiO_2暴露组,每组7只,暴露组剂量设置分别为13.64、27.27、40.91、54.55、68.18 mg/kg(以体重计,余同)。每3 d气管滴注一次,染毒28 d。肺功能仪监测气管滴注前后肺功能变化,采用多功能酶标仪测定肺泡灌洗液中总蛋白质量浓度(下称浓度)、乳酸脱氢酶活性、碱性磷酸酶活性,HE染色观察肺组织病理损伤。[结果]暴露组大鼠体重增长均较空白对照组降低(P<0.05)。54.55、68.18 mg/kg N-nTiO_2暴露组大鼠每分通气量高于空白对照组(P<0.05),40.91 mg/kg及以上N-nTiO_2暴露组的最大呼气流量高于空白对照组(P<0.05),68.18 mg/kg N-nTiO_2暴露组的潮气量、最大吸气流量高于空白对照组(P<0.05)。与空白对照组相比,仅40.91 mg/kg N-nTiO_2暴露组大鼠肺泡灌洗液中总蛋白浓度增高(P<0.05),27.27 mg/kg及以上N-nTiO_2暴露组乳酸脱氢酶活性升高(P<0.05),54.55 mg/kg以上N-nTiO_2暴露组碱性磷酸酶活性升高(P<0.05)。肺病理组织学检测结果显示,染毒大鼠肺组织主要表现为细胞增生、充血、炎性细胞浸润、肺阻塞、肺不张及肺实变等,且随着染毒剂量的增加,肺组织损伤程度也逐渐加重。[结论]经气管滴注N-nTiO_2后会引起大鼠肺部病理损伤及肺功能降低。[Objective] To investigate the pulmonary injury induced by novel nano materials, nitrogen-doped nano titanium dioxide（N-nTiO2）.[Methods] Forty-two specific-pathogen-free SD rats were divided into one blank control group and five N-nTiO2 groups（13.64, 27.27, 40.91, 54.55, and 68.18 mg/kg, respectively, in terms of body weight thereafter）, with seven rats in each group. The rats were exposed to N-nTiO2 by intratracheal instillation every three days and for 28 days. Lung function changes were monitored with lung function measurement instrument, the quantity of total protein and activities of lactate dehydrogenase and alkaline phosphatase in bronchoalveolar lavage fluid were measured with multi-mode enzyme-labelled meter, and the lung histopathological damage was observed using HE staining.[Results] The body weight gain was less in each N-nTiO2 group compared with the blank control group（P 〈 0.05）. The minute ventilation volume significantly increased in the 54.55 and 68.18 mg/kg N-nTiO2 groups compared with the blank control group（P 〈 0.05）, the peak expiratory flow significantly increased in the 40.91 mg/kg and above N-nTiO2 groups（P 〈 0.05）, and the tidal volume and peak expiratory flow significantly increased in the 68.18 mg/kg N-nTiO2 group（P 〈 0.05）. Compared with the blank control group, the quantity of total protein significantly increased only in the 40.91 mg/kg N-nTiO2 group（P 〈 0.05）, the enzyme activity of lactate dehydrogenase increased in the 27.27 mg/kg and above N-nTiO2 groups, and the enzyme activity of alkaline phosphatase increased in the 54.55 mg/kg and above N-nTiO2 groups（P 〈 0.05）. The results of lung histopathological examination results demonstrated that lung tissue injury was aggravated in the groups treated with higher levels of N-nTiO2, such as cell proliferation, hypermia, and inflammatory cell infiltration, as well as lung obstruction, atelectasis, and consolidation.[Conclusion] Intratracheal instillation of N-nTiO2 may induce not only organic

关 键 词：氮杂纳米二氧化钛 气管滴注 肺功能 肺泡灌洗液 肺毒性 

分 类 号：R13[医药卫生—劳动卫生]