基于基因集富集分析阐释补肺益肾方抑制巨噬细胞炎症反应机制  

Investigating Interventional Mechanism of Bufei Yishen Formula for Inhibiting Macrophage Inflammatory Response Based on Gene Set Enrichment Analysis

作　　者：关庆洲 赵鹏 田燕歌[1,2] 李康沉 彭岩 郭弘妍 李建生[1,5] GUAN Qingzhou;ZHAO Peng;TIAN Yange;LI Kangchen;PENG Yan;GUO Hongyan;LI Jiansheng(Henan Key Laboratory of Chinese Medicine for Respiratory Disease,Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province and Education Ministry of P.R.China,Henan University of Chinese Medicine,Zhengzhou 450046,China;Academy of Chinese Medical Sciences,Henan University of Chinese Medicine,Zhengzhou 450046,China;National Engineering Research Center for Bejing Biochip Technology,Beijing 102200,China;Bejing CapitalBio Pharma Technology Co,Ltd.,Bejing 102200,China;the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学呼吸疾病中医药防治省部共建协同创新中心、河南省中医药防治呼吸病重点实验室,郑州450046 [2]河南中医药大学中医药科学院,郑州450046 [3]生物芯片北京国家工程研究中心,北京102200 [4]北京博奥晶方生物科技有限公司,北京102200 [5]河南中医药大学第一附属医院,郑州450000

出　　处：《世界科学技术-中医药现代化》2024年第6期1490-1496,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家中医药管理局中医药传承与创新“百千万”人才工程—岐黄工程首席科学家(国中医药人教函[2021]7号),负责人:李建生;国家自然科学基金委员会面上项目(81973822):基于组分配伍探讨补肺益肾方阻抑炎症反应治疗COPD机制,负责人:李建生;人力资源和社会保障部、全国博士后管理委员会博士后创新人才支持计划(BX20200115):基于转录组定性特征识别COPD预警标志并探讨补肺益肾组分方治疗机制,负责人:关庆洲。

摘　　要：目的从通路水平探究慢性阻塞性肺疾病有效方药补肺益肾方的干预机制。方法采用LPS诱导巨噬细胞建立炎症反应模型。基于基因集富集分析(Gene set enrichment analysis,GSEA)方法,筛选巨噬细胞炎症反应相关通路,通过富集评分(Normalized enrichment score,NES)筛选药物干预后发生逆转的通路,揭示补肺益肾方及其配伍的干预机制。结果补肺益肾方所含中药的NES为-1377.23,其中补肾配伍的为-485.07、活血配伍的为-351.86、化痰配伍的为-303.71、益气配伍的为-236.59;补肺益肾方显著逆转的通路为213条,其中活血配伍的为184条、补肾配伍的为147条、化痰配伍的为134条、益气配伍的为133条,逆转率分别为75.41%、60.25%、54.92%、54.51%。TGF-βproduction等90条通路在4个配伍中均被显著逆转。Positive regulation of cytokine production involved in inflammatory response等为配伍特异性逆转通路。结论补肺益肾方各配伍组逆转炎症信号通路的强度依次为补肾、活血、化痰、益气配伍,逆转通路数量依次为活血、补肾、化痰、益气。补肺益肾方可通过调控各配伍共性及特异性逆转通路干预炎症反应。Objective To explore the interventional mechanism of Bufei Yishen formula on chronic obstructive pulmonary disease from pathway level.Methods Macrophage inflammatory model was established by LPS stimulation.Based on gene set enrichment analysis(GSEA)method,macrophage inflammation related pathways were screened,and normalized enrichment score(NES)was used to identify pathways that were reversed by traditional Chinese medicine treatment,revealing the interventional mechanism of Bufei Yishen formula and its compatibility.Results The NES of Bufei Yishen formula was-1377.23,among which the NES of Bushen compatibility was-485.07,that of Huoxue was-351.86,Huatan was-303.71,and Yiqi was-236.59.There were 213 significantly disturbed pathways reversed after the intervention of Bufei Yishen formula,among which there were 184 reversed pathways for Huoxue compatibility,147 reversed pathways for Bushen,134 reversed pathways for Huatan,133 reversed pathways for Yiqi,and the reversal rate was 75.41%,60.25%,54.92%,54.51%,respectively.90 pathways,including TGF-βproduction,were significantly reversed in the four compatibilities.Positive regulation of cytokine production involved in inflammatory response etc were specifically reversed pathways for compatibility.Conclusion The intensity of Bufei Yishen formula that reversed macrophage-inflammatory related pathways was in order of Bushen,Huoxue,Huatan and Yiqi compatibility.And the number of pathways that could be reversed by the compatibility of Bufei Yishen formula was Huoxue,Bushen,Huatan and Yiqi.Bufei Yishen formula could regulate the common and specific reversal pathways of the compatibilities to intervene the inflammatory response.

关 键 词：慢性阻塞性肺疾病 补肺益肾方 巨噬细胞 炎症反应 基因集富集分析 

分 类 号：R285.5[医药卫生—中药学]