转录组学结合蛋白质组学筛选罗汉果皂苷V缓解OVA诱导哮喘小鼠的关键通路

Transcriptomic and proteomic screening of key pathways of mogroside V relieving OVA-induced mouse asthma

目的基于转录组学和蛋白质组学,探讨罗汉果皂苷V缓解哮喘小鼠肺部炎症的潜在关键机制。方法采用卵清蛋白(ovalbumin,OVA)诱导雌性BALB/C小鼠哮喘,给予罗汉果皂苷V,观察肺部组织及其病理变化。选择空白组、模型组和罗汉果皂苷V给药组,分别每组3个样本进行转录组学和蛋白质组学分析,筛选出差异基因和差异蛋白,对其进行趋势分析,再对所有趋势基因和趋势蛋白进行KEGG富集分析。结果肺组织形态学和HE染色结果显示,罗汉果皂苷V缓解OVA诱导的肺部炎症。基于组学分析发现,在1122个趋势基因中,空白与模型组比较上调且模型与给药组比较下调的基因有454个,反之,有111个;在497个趋势蛋白中,空白与模型组比较上调且模型与给药组比较下调的差异表达基因有238个,反之,有91个。基于转录组和蛋白质组趋势分析其KEGG富集到PI3K/Akt信号通路,经分子生物学方法验证其关键因子Igha、Ighg1、PI3K及Akt在模型组升高且在给药组降低。结论基于转录组学和蛋白质组学的方法揭示罗汉果皂苷V可能通过抑制PI3K/Akt信号通路的激活,改善哮喘小鼠肺部炎症,发挥润肺止咳的作用,本研究为治疗哮喘的药物开发提供实验参考。

Aim To discuss the potential key mechanism of mogroside V in relieving pulmonary inflammation in asthmatic mice based on transcriptomics and proteomics.Methods Ovalbumin(OVA)was chosen to induce female BALB/C mouse asthma model,and the mice were treated with mogroside V to observe the pathological changes of lung tissues.Lung tissues in groups of natural control,ovalbumin control and mogroside V control were chosen for transcriptomic and proteomic analysis,and differential genes and proteins were screened for tendency analysis,followed by KEGG enrichment analysis for the potential genes and proteins.Results The results of lung morphological observation and HE revealed that mogroside V attenuated the OVA-induced pulmonary inflammation.Differential genes and proteins were selected from RNA-seq and DIA analysis.In the analysis of omics 454 genes increased in comparison between groups of natural control with ovalbumin control and decreased in comparison between groups of mogroside V control with ovalbu-min control in 1122 potential genes,and 111 genes were of opposite features.A total of 238 proteins increased in comparison between groups of natural control with ovalbumin control and decreased in comparison between groups of mogroside V control with ovalbumin control in 497 potential proteins,and 91 proteins were of opposite features.The PI3K/Akt signaling pathway was enriched from KEGG and tendency analysis of transcriptomics and proteomics.The key factors of Igha,Ighg1,PI3K and Akt increased in ovalbumin control group and decreased in mogroside V control group by the validation of molecualr biology experiments.Conclusions Transcriptomic and proteomic analysis exhibits that mogroside V relieves asthma in mice through inhibiting the activation of key factors including Lgha,Lgh1,PI3K and Akt,depressing the signaling pathway,attenuating pulmonary inflammation to reach the goal of moistening lung and relieve cough,which provides a reference for drug development of asthma.