基于转录组学及肠道菌群角度探讨支气管哮喘不同证型之间的内在差异  

Exploring the intrinsic differences among different evidence types of bronchial asthma from transcriptomics and intestinal flora perspectives

作　　者：张晶[1] 岳莉 陈铃 敬馨 应伟林 张博达[1] ZHANG Jing;YUE Li;CHEN Ling;JING Xin;YING Weilin;ZHANG Boda(The Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan 637002,China)

机构地区：[1]川北医学院附属医院中医科,四川南充637002

出　　处：《中国微生态学杂志》2025年第3期249-259,共11页Chinese Journal of Microecology

基　　金：教育部产学合作项目(220904439083508);川北医学院附属医院2021年度院内课题(2021LC012)。

摘　　要：目的 探索支气管哮喘不同证型间转录组学和肠道菌群差异,揭示支气管哮喘脾虚证、气虚证、阳虚证、阴虚证的内在机制。方法 将30只SPF级SD大鼠(3~4周龄,体重60~70 g)随机分为对照组、脾虚组、阴虚组、阳虚组、气虚组,每组6只。除对照组以外,其余四组分别采用不同的复合因素方法对大鼠进行造模,造模3周后进行取材,收集肺组织进行转录组分析,粪便进行肠道菌群16S rRNA基因高通量测序。结果 通过肺组织转录组分析发现与对照组相比,脾虚组基因显著富集在细胞分裂等过程,以及Graft-versus-host disease等信号通路上;气虚组基因显著富集在白细胞介导的细胞毒性的调节等过程,以及Ribosome等信号通路上;阳虚组基因显著富集在病毒基因组复制的负调控等过程,以及Viral protein interaction with cytokine and cytokine receptor等信号通路上;阴虚组基因显著富集在多巴胺分泌等过程,以及Glycosaminoglycan binding proteins等信号通路上。通过微生物群落高通量测序发现,在所有组别的门水平上,厚壁菌门和拟杆菌门为主要优势菌群,紧随其后的是蓝藻菌门、变形菌门、放线菌门。与对照组相比,气虚组显示厚壁菌门相对丰度下降而拟杆菌门相对丰度上升的趋势;相反,阳虚组、阴虚组及脾虚组则表现为厚壁菌门相对丰度增加,拟杆菌门相对丰度降低(F=3.153,P=0.037)。与对照组相比,气虚组厚壁菌门/拟杆菌门(F/B)比值降低,阴虚组、阳虚组、气虚组F/B比值增高,但差异无统计学意义(F=2.197,P=0.106)。在所有组别的属水平上,普氏菌属、乳杆菌属、瘤胃球菌属为主要优势菌群,阳虚组、阴虚组、气虚组、脾虚组大鼠肠道菌群在属水平上最大丰度排名前20位的物种总丰度降低。结论 支气管哮喘不同证型之间存在生物学差异,为临床上治疗不同证型支气管哮喘提供潜在治疗靶点。Objective To explore the differences in transcriptomics and intestinal flora among different syndromes of bronchial asthma,and reveal the intrinsic mechanisms of the four syndromes of bronchial asthma,namely spleen deficiency,qi deficiency,yang deficiency and yin deficiency.Methods Thirty SPF-grade SD rats(3-4 weeks old,weighing60-70 g) were randomly divided into the control group,spleen-deficient group,yin-deficient group,yang-deficient group,and qi-deficient group,with six rats in each group.Except for the control group,the rats in the other four groups were modelled using different composite factor methods.3 weeks after modelling,the rats were sampled,lung tissues were collected for transcriptome analysis,and faeces were subjected to high-throughput sequencing of the 16S rRNA gene of the intestinal flora.Results Transcriptome analysis of lung tissue revealed that compared with the control group,the genes in the spleen-deficiency group were significantly enriched in the processes such as cell division and signaling pathways such as Graft-versus-host disease;the genes in the qi-deficiency group were significantly enriched in the processes such as leukocyte-mediated cytotoxicity and signaling pathways such as Ribosome;the genes in the yang-deficiency group were significantly enriched in the processes such as negative regulation of replication and signaling pathways such as viral genome.The genes in the yang-deficiency group were significantly enriched in the processes such as negative regulation of replication and signaling pathways such as viral protein interaction with cytokine and cytokine receptor;the genes in the yin-deficiency group were significantly enriched in the processes such as dopamine secretion and signaling pathways such as Glycosaminoglycan binding proteins.High-throughput sequencing of microbial communities revealed that at the phylum level in all groups,the phylum Firmicutes and Bacteroidetes were the main dominant phyla,followed closely by Cyanobacteria,Aspergillus and Actinobacteria.Compared

关 键 词：支气管哮喘 中医证候 转录组学 肠道菌群 

分 类 号：R256.12[医药卫生—中医内科学]