纳米铟锡氧化物致SD大鼠肺泡蛋白沉积症的机制研究  

Mechanism of nano-indium-tin oxide inducing pulmonary alveolar proteinosis in Sprague-Dawley rats

作　　者：刘楠 周春玲 蔚岩 曹福源 李清钊 肖经纬[3] 李斌[3] 关维俊 姚三巧 Liu Nan;Zhou Chunling;Yu Yan;Cao Fuyuan;Li Qingzhao;Xiao Jingwei;Li Bin;Guan Weijun;Yao Sanqiao(School of Public Health,North China University of Science and Technology,Hebei Coal Mine Health and Safety Laboratory,Tangshan 063000,China;Laboratory Animal Center,North China University of Science and Technology,Tangshan 063000,China;Institute of Occupational Health and Poisoning Control,Chinese Center for Disease Control and Prevention,Beijing 100050,China;Xinxiang Medical University,Xinxiang 453003,China)

机构地区：[1]华北理工大学公共卫生学院,河北省煤矿卫生与安全实验室,唐山063000 [2]华北理工大学实验动物中心,唐山063000 [3]中国疾病预防控制中心职业卫生与中毒控制所,北京100050 [4]新乡医学院,453003

出　　处：《中华劳动卫生职业病杂志》2020年第11期815-818,共4页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家公益性卫生行业科研专项(201402021);华北理工大学2019年研究生创新项目(2019B17)。

摘　　要：目的探讨纳米铟锡氧化物染毒致大鼠肺泡蛋白沉积症的发病机制,为进一步制定铟职业接触限值以及防护措施提供依据。方法于2018年8月,选择6~8周龄SPF级SD雄性大鼠40只,体重(200±10)g,随机分为对照组、低剂量组(1.2 mg/kg)、中剂量组(3 mg/kg)和高剂量组(6 mg/kg),每组10只。常规饲养1周,给予非暴露式气管灌注染毒,每周2次,间隔3 d,连续染毒12周。染毒期间每周称量体重,观察体重变化;染毒结束后水合氯醛麻醉处死,留取肺组织、血清;肺组织进行苏木精-伊红(HE)和过碘酸雪夫(PAS)染色,观察病理结果;电感耦合等离子体质谱法测定血清铟含量;酶联免疫吸附法测定肺组织中肺表面活性蛋白A(SP-A)、肺表面活性蛋白D(SP-D)、Ⅱ型肺泡细胞表面抗原6(KL-6)和血清中粒细胞-巨噬细胞集落刺激因子(GM-CSF)含量。结果病理结果显示,气管灌注纳米铟锡氧化物后,对照组大鼠肺泡结构基本完整,各剂量染毒组大鼠肺泡腔内可见均匀一致、嗜伊红的无结构细颗粒状物质,有巨噬细胞增生并且可见巨噬细胞增多,以高剂量组较明显。对照组大鼠PAS染色阴性,各剂量染毒组大鼠肺组织中均可见PAS染色阳性物质。各剂量染毒组大鼠血清铟含量均明显高于对照组,差异均有统计学意义(P<0.05)。与对照组比较,各剂量染毒组大鼠肺组织中SP-A、SP-D和KL-6均明显升高,血清中GM-CSF均明显降低,差异均有统计学意义(P<0.05)。结论大鼠肺泡蛋白沉积症可能与纳米铟锡氧化物致肺泡巨噬细胞破坏,巨噬细胞对表面活性物质代谢清除障碍,引起大量肺泡表面活性物质聚集有关。Objective To investigate the pathogenesis of pulmonary alveolar proteinosis in rats induced by nano-indium-tin oxide exposure,and to provide a basis for further determining the limit of occupational exposure to indium and developing related protection measures.Methods In August 2018,a total of 40 specific pathogen-free Sprague-Dawley rats,with an age of 6-8 weeks and a body weight of(200±10)g,were randomly divided into control group,low-dose group(1.2 mg/kg),middle-dose group(3 mg/kg),and high-dose group(6 mg/kg),with 10 rats in each group.After 1 week of routine feeding,the rats were given non-exposed intratracheal instillation twice every week,with an interval of 3 days,for 12 consecutive weeks.Body weight was measured every week during exposure to observe the change in body weight;The rats were anesthetized and sacrificed by chloral hydrate after the exposure ended,and lung tissue and serum were collected;Hematoxylin-eosin staining and periodic acid-Schiff(PAS)staining were performed for lung tissue to observe pathological results;Inductively coupled plasma mass spectrometry was used to measure the serum level of indium;ELISA was used to measure the levels of surfactant protein A(SP-A),surfactant protein D(SP-D),and the type II alveolar cell surface antigen Krebs von den Lungen-6(KL-6)in lung tissue and the serum level of granulocyte-macrophage colony-stimulating factor(GM-CSF).Results The pathological results showed that the rats in the control group had basically complete alveolar structure,and after intratracheal instillation of nano indium-tin oxide,uniform,eosinophilic,and unstructured granular substances were observed in the alveolar space of the low-,middle-,and high-dose exposure groups,with macrophage proliferation and an increase in macrophages,especially in the high-dose group.Negative PAS staining was observed in the control group,while substances with positive PAS staining were observed in lung tissue in each exposure group.The three exposure groups had a significantly higher serum level of indiu

关 键 词：大鼠 肺泡蛋白沉积症 纳米铟锡氧化物 铟 肺表面活性物质相关蛋白质类 

分 类 号：R114[医药卫生—卫生毒理学]