Mechanism of Exosome-Induced Viral Asthma Model Based on Transcriptomics and Potential Traditional Chinese Medicine Intervention
Objective:This study aimed to explore the role of exosomes after respiratory syncytial virus(RSV)intervention in the pathogenesis of asthma and potential mechanisms of traditional Chinese medicine(TCM)intervention based on transcriptomics.Methods:Exosomes were ex-tracted from bone marrow mesenchymal stem cells after RSV intervention,then transmission electron microscopy,nanoparticle tracking analysis(NTA)and Western blot were used to identify the morphology and markers of exosomes.Twenty-four SPF grade male C57 mice were random-ly divided into blank control group,RSV group,and exosome group.After modeling for 3 weeks,lung function was measured and pathological staining was performed to verify the presence of pathological changes of asthma.High-throughput transcriptome sequencing(RNA-seq)was conducted on mouse airway tissues to identify differentially expressed genes(DEGs).Finally,potential TCM key targets were predicted and summarized using integrated pharmacological methods.Results:Transmission electron microscopy showed that exosomes exhibited a typical double-layered membrane structure,with an average diameter of 133.1 nm as determined by NTA.Western blot detected the expression of ex-osomal membrane marker proteins CD63,CD9 and TSG101.Compared with the blank control group,both the RSV group and exosome group showed a significant decrease in forced vital capacity(FVC)(P＜0.05)and a marked decrease in dynamic lung compliance(Cdyn)(P＜0.01).The peak expiratory flow(PEF)was decreased in the RSV group(P＜0.05)and it was significantly decreased in exosome group(P＜0.01).Compared with blank control group,the Lung resistance(RL)was significantly increased in the RSV group and exosome group(P＜0.01).There was no statistically significant differences in lung function indices between the RSV group and exosome group(P＞0.05).In terms of inflammation infiltration and airway mucus secretion,the mice in the exosome group exhibited inflammatory cell infiltration and eosin-ophil infiltration,while those in RSV group mainly showed neutrophil and lymphocyte infiltration,with significantly more goblet cell mucus se-cretion than in the exosome group.The sequencing results of airway epithelium suggested that DEGs among the three groups were mainly en-riched in the immune,nervous,and endocrine systems,with common enriched pathways including peroxisome proliferator-activated receptor,interleukin 17,and ECM-receptor interaction signaling pathways.The predicted potential TCM were mainly heat-clearing medicinal,tonifying medicinal and qi-regulating and blood-activating medicinal,whose components could act on multiple targets and pathways to regulate asthma neuroendocrine and immune balance.Conclusion:Exosomes after RSV intervention could induce pathological changes of asthma,such as air-way inflammation and airway remodeling.TCM exerted an overall regulatory effect from multiple aspects,multiple targets,and multiple sys-tems.
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维普
