大鼠尘肺病模型肠道与呼吸道共有差异菌群和代谢产物相关性研究  

Correlation between intestinal and respiratory flora and their metabolites in a rat pneumoconiosis model

作　　者：阚霖慧 徐鑫 陈雨萌 王儇墨 李金龙 沈福海 Kan Linhui;Xu Xin;Chen Yumeng;Wang Xuanmo;Li Jinlong;Shen Fuhai(School of Public Health,North China University of Technology,Coal Mine Health and Safety Laboratory of Hebei Province,Tangshan 063210,China;School of Jitang,North China University of Technology,Tangshan 063210,China;Oriental College of Beijing University of Traditional Chinese Medicine,Cangzhou,061113,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063210 [2]华北理工大学冀唐学院,唐山063210 [3]北京中医药大学东方学院,沧州061113

出　　处：《中华劳动卫生职业病杂志》2023年第1期21-30,共10页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：河北省教育厅高等学校科学技术研究项目(ZD2018226);河北省自然科学青年基金项目(H2019209576)。

摘　　要：目的筛选大鼠肠道和呼吸道共有差异菌群和差异代谢物,分析大鼠肠道菌群和代谢物的变化在大鼠尘肺病进展中可能的作用。方法于2020年4月,将18只SD大鼠随机分为3组(对照组、煤矿粉尘组和二氧化硅组,每组各6只)。煤矿粉尘组和二氧化硅组大鼠采用非气管暴露法分别灌注1 ml 50 mg/ml煤矿井下粉尘悬浊液和二氧化硅悬浊液,对照组大鼠灌注同等剂量灭菌生理盐水。染尘24周后采集大鼠粪便、咽拭子和肺灌洗液。采用16SrDNA基因测序技术和UHPLC-QTOF-MS非靶向代谢组学技术检测各组大鼠粪便、咽拭子和肺灌洗液中菌群和代谢物,筛选肠道和呼吸道共有差异菌群和共有差异代谢物。并采用Spearman法对差异菌群和代谢物进行相关性分析。结果与对照组比较,煤矿粉尘组门水平下共筛选到9种肠道和呼吸道共有差异菌群,属水平下共筛选到9种肠道和呼吸道共有差异菌属,主要为厚壁菌门、放线菌门、链球菌属、乳杆菌属;与对照组比较,二氧化硅组门水平下共筛选到9种共有差异菌群,属水平下共筛选到5种共有差异菌群,主要为变形菌门、放线菌门、异杆菌属、粘液杆菌属。与对照组比较,煤矿粉尘组共筛出7种共有差异代谢物,标桩菌素、芳樟醇氧化物和异亮氨酸-亮氨酸在肠道和呼吸道中均上调;二氧化硅组与对照组比较,共筛出19种共有差异代谢物,其中二乙醇胺、1-氨基环丙烷羧酸、异亮氨酸-亮氨酸、鞘氨醇、棕榈酸、二氢鞘氨醇、1,2-二油酰基-sn-甘油-3-磷脂酰胆碱、1-硬脂酰-2-油酸甘油酯磷酸化胆碱在肠道和呼吸道中均上调。结论尘肺病大鼠肠道和呼吸道菌群存在移位现象,大鼠在尘肺病进展过程中存在脂质代谢失衡。Objective Differential flora and differential metabolites shared by the intestinal and respiratory tracts of rats were screened to analyze the possible role of changes in intestinal flora and metabolites in the progression of pneumoconiosis in rats.Methods In April 2020,18 SD rats were randomly divided into three groups(control group,coal mine dust group and silica group,6 in each group),rats in the coal mine dust group and silica group were perfused with 1 ml of 50 mg/ml coal mine well dust suspension and silica suspension by nontracheal exposure,respectively.While rats in the control group were perfused with an equal dose of sterilized normal saline.Twenty four weeks after dust staining,rat feces,throat swabs,and lung lavages were collected.16SrDNA gene sequencing and UHPLC-QTOF-MS untargeted metabolomics were used to analyze the flora and metabolites in feces,throat swabs and lung lavage fluid of rats in each group,to screen for shared differential flora and shared differential metabolites in intestinal and respiratory tract,and the correlation analysis between the differential flora and metabolites was performed using Spearman's statistics.Results Compared with the control group,a total of 9 species shared differential flora between intestinal and respiratory tract were screened at phylum level,and a total of 9 species shared differential genus between intestinal and respiratory tract were screened at genus level in the coal mine dust group,mainly Firmicutes,Actinobacteria,Streptococcus,Lactobacillus,etc.Compared with the control group,a total of 9 shared differential flora were screened at the phylum level,and a total of 5 shared differential genus were screened at the genus level in the silica group,mainly Proteobacteria,Actinobacteria,Allobactera,Mucilaginibacter,etc.Compared with the control group,a total of 7 shared differential metabolites were screened for up-regulation of Stigmatellin,Linalool oxide and Isoleucine-leucine in both intestinal and respiratory tract in the coal mine dust group.Compared wi

关 键 词：尘肺病 菌群 代谢产物 纤维化 

分 类 号：R135.2[医药卫生—劳动卫生] R-332[医药卫生—公共卫生与预防医学]