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[大鼠尘肺模型中肠道与呼吸道菌群及其代谢产物之间的相关性]

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

作者信息

Kan L H, Xu X, Chen Y M, Wang X M, Li J L, Shen F H

机构信息

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.

出版信息

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2023 Jan 20;41(1):21-30. doi: 10.3760/cma.j.cn121094-20211011-00495.

DOI:10.3760/cma.j.cn121094-20211011-00495
PMID:36725290
Abstract

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. 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. 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 with the control group , a total of 19 shared differential metabolites werescreened in the silica group, of which Diethanolamine, 1-Aminocyclopropanecarboxylic acid, Isoleucine-leucine, Sphingosine, Palmitic acid, D-sphinganine, 1, 2-dioleoyl-sn-glycero-3-phosphatidylcholine, and 1-Stearoyl-2-oleoyl-sn-glycerol 3-phosphocholine were up-regulated in both the intestinal and respiratory tract. There is a translocation of intestinal and respiratory flora in pneumoconiosis rats, and rats have an imbalance of lipid metabolism during the progression of pneumoconiosis.

摘要

筛选大鼠肠道和呼吸道共有的差异菌群和差异代谢物,以分析肠道菌群和代谢物变化在大鼠尘肺病进展中的可能作用。2020年4月,将18只SD大鼠随机分为三组(对照组、煤矿粉尘组和二氧化硅组,每组6只),煤矿粉尘组和二氧化硅组大鼠分别经非气管暴露灌注1 ml 50 mg/ml煤矿井粉尘悬浮液和二氧化硅悬浮液,而对照组大鼠灌注等量的灭菌生理盐水。染尘24周后,收集大鼠粪便、咽拭子和肺灌洗液。采用16SrDNA基因测序和UHPLC-QTOF-MS非靶向代谢组学分析各组大鼠粪便、咽拭子和肺灌洗液中的菌群和代谢物,筛选肠道和呼吸道共有的差异菌群和差异代谢物,并采用Spearman统计方法进行差异菌群与代谢物之间的相关性分析。与对照组相比,煤矿粉尘组在门水平筛选出肠道和呼吸道共有的差异菌群共9种,在属水平筛选出肠道和呼吸道共有的差异菌属共9种,主要为厚壁菌门、放线菌门、链球菌属、乳杆菌属等。与对照组相比,二氧化硅组在门水平筛选出共9种差异菌群,在属水平筛选出共5种差异菌属,主要为变形菌门、放线菌门异杆菌属、黏液杆菌属等。与对照组相比,煤矿粉尘组在肠道和呼吸道均筛选出共7种差异代谢物上调,包括柱晶白霉素、氧化芳樟醇和异亮氨酸-亮氨酸。与对照组相比,二氧化硅组共筛选出19种差异代谢物,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、D-二氢鞘氨醇、1,2-二油酰基-sn-甘油-3-磷脂酰胆碱和1-硬脂酰-2-油酰基-sn-甘油-3-磷酸胆碱在肠道和呼吸道均上调。尘肺病大鼠存在肠道和呼吸道菌群易位,且在尘肺病进展过程中大鼠存在脂质代谢失衡。

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