长期电子烟或传统香烟暴露的小鼠肺脏转录组学差异分析

Differential analysis of lung transcriptome in mice exposed to long-term electronic cigarettes or conventional cigarettes

目的探讨长期电子烟或传统香烟暴露对小鼠肺组织转录组学的影响。方法将30只C57BL/6小鼠随机分为正常对照组、传统香烟组、电子烟组,每组10只,传统香烟组及电子烟组分别给予同等条件下被动吸烟6个月。检测肺功能,收取肺组织,部分肺组织进行石蜡包埋,制作病理切片,苏木素-伊红(HE)染色后观察小鼠肺组织病理形态;另外肺组织进行转录组学检测,生物信息学分析筛选差异基因,并进行差异基因GO及KEGG通路功能富集分析。结果相较正常对照组,传统香烟组50 ms用力呼气容积(FEV0.05)、FEV0.05/用力肺活量(FVC)显著降低(P<0.05);电子烟组FEV0.05、FVC、FEV0.05/FVC显著降低(P<0.05)。肺组织病理学提示,传统香烟组及电子烟组肺泡腔均存在明显的扩张及炎性细胞的浸润;转录组学检测结果显示传统香烟组发现1089个差异基因,电子烟组发现1044个差异基因,差异基因功能富集分析显示传统香烟组和电子烟组差异基因多分布在胞质细胞器结构上,生物学过程主要聚类在生物调节、细胞转化、发育过程、代谢过程、多生物学过程及应激反应;分子功能学主要聚类在黏附和催化活性分子功能学过程,多通过运输与代谢、信号传导、翻译及免疫系统等信号通路进行作用。结论长期电子烟暴露可导致肺功能下降及肺组织肺泡腔的扩大,炎性细胞的浸润,导致肺结构变化。转录组学检测分析可为电子烟导致肺功能学及病理学改变的潜在机制提供理论基础。

Objective To investigate the effects of long-term exposure to electronic cigarettes or conventional cigarettes on the transcriptome of lung tissue in mice.Methods Thirty C57BL/6 mice were randomly divided into normal control group,traditional cigarette group and electronic cigarette group,with ten mice in each group.The traditional cigarette group and electronic cigarette group were given passive smoking for 6 months under the same conditions.The lung function of three groups were detected.The lung tissue of mice was collected,part of lung tissue was embedded in paraffin wax to make the pathological slice,pathological morphology in the lung tissue in mice was observed by hematoxylin-eosin(HE)staining.In addition,lung tissues were detected by transcriptomics and screened for differential genes by bioinformatics analysis,and differential genes were screened for GO and KEGG pathway function enrichment analysis.Results Compared with the normal control group,50 ms forced expiratory volume(FEV0.05),FEV0.05/forced vital capacity(FVC)were significantly decreased in traditional cigarette group(P<0.05),FEV0.05,FVC and FEV0.05/FVC were significantly decreased in electronic cigarette group(P<0.05).Pulmonary pathology suggested that the alveolar cavity of both traditional cigarette group and electronic cigarette group had obvious dilatation and inflammatory cell infiltration.Transcriptomics test result revealed 1089 differentially genes in the traditional cigarette group and 1044 differentially genes in the electronic cigarette group.Differential gene function enrichment analysis showed that in both the traditional cigarette group and the electronic cigarette group,the differential genes were mostly distributed in the cytoplasmic organelle structure,biological processes were mainly clustered in biological regulation,cell transformation,developmental process,metabolic process,multibiological process and stress response.Molecular functionology mainly focused on the molecular functionology processes of adhesion and catalytic activity,and functions mainly through signaling pathways such as transport and metabolism,signal transduction,translation and immune system.Conclusions Long-term electronic cigarette exposure could lead to the decline of lung function and lung tissue alveolar cavity expansion,inflammatory cell infiltration,resulting in changes in lung structure.Transcriptome analysis could provide a theoretical basis for the potential mechanism of lung function and pathological changes caused by electronic cigarette.