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-β production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.
Abstract
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-β production,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.
基金项目
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)
国家自然科学基金委员会面上项目(81973822)
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)
国家科技期刊平台
NSTL
万方数据