基于GC-MS的枳壳水煎液抑制THP-1源性巨噬细胞泡沫化代谢组学研究  

Metabolomics study of GC-MS-based Aurantii Fructus water decoction inhibition of THP-1-derived macrophage foaming

作　　者：柯畅 王燕 曹国胜 周仲实 刘艳菊 涂济源 KE Chang;WANG Yan;CAO Guosheng;ZHOU Zhongshi;LIU Yanju;TU Jiyuan(School of Pharmacy,Hubei University of Chinese Medicine,Wuhan 430065,China;Hubei Research Center for Processing Technology of Traditional Chinese Medicine,Wuhan 430065,China)

机构地区：[1]湖北中医药大学药学院,武汉430065 [2]湖北省中药炮制技术工程研究中心,武汉430065

出　　处：《中华中医药杂志》2024年第3期1522-1527,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：湖北中医药大学“青苗计划”资助项目(No.2021ZZX012);中药炮制技术传承基地项目(No.鄂中医通[2022]2号)。

摘　　要：目的:研究枳壳水煎液(AFD)抑制氧化低密度脂蛋白(ox-LDL)诱导的人单核白血病细胞(THP-1)源性巨噬细胞泡沫化的代谢组学及其可能机制。方法:THP-1细胞分为对照组,模型组,枳壳低、中、高剂量组。采用油红O染色法检测泡沫细胞的形成,用ELISA法检测细胞内甘油三酯(TG)、总胆固醇(TC)及炎症因子水平[单核细胞趋化蛋白1(MCP-1)、干扰素γ(IFN-γ)和肿瘤坏死因子α(TNF-α)],采用GC-MS检测各组细胞代谢组,寻找与药效相关的差异代谢物,并预测相关代谢通路。结果:AFD可抑制泡沫细胞形成,降低TG、TC及炎症因子MCP-1、IFN-γ、TNF-α表达水平(P<0.01,P<0.05)。代谢组学分析显示,L-丝氨酸、L-苏氨酸、L-甲硫氨酸等7种生物标志物与细胞泡沫化关系密切,给药后显著回调(P<0.05,P<0.01)。结论:AFD可通过调节甘氨酸/丝氨酸代谢、鞘脂代谢、甲硫氨酸代谢抑制巨噬细胞泡沫化,为动脉粥样硬化的治疗提供依据。Objective:To study the metabolomics and possible mechanism of the water detection of Auranti Fructus(AFD)inhibiting the foaming of THP-1-derived macrophages induced by ox-LDL.Methods:THP-1 cell was divided into control group,model group,low-dose,middle-dose and high-dose groups.Oil red O staining was used to detect the formation of foam cells,ELISA was used to detect the levels of intracellular triglyceride(TG),total cholesterol(TC)and infammatory factors[monocyte chemoattractant protein-1(MCP-1),interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-a)],and GC-MS was used to detect the cell metabolome in each group to find the differential metabolites related to drug efficacy,and predict related metabolic pathways.Results:AFD could inhibit foam cellformation and reduce the expression levels of TG,TC,MCP-1,IFN-γ,TNF-α(P<0.01,P<0.05).Metabolomics analysis showed that 7 biomarkers including L-serine,L-threonine,and L-methionine were closely related to cell foaming,and were significantly reversed after administration(P<0.05,P<0.01).Conclusion:AFD can inhibit cell foaming of macrophages by regulating glycine/serine metabolism,sphingolipid metabolism and methionine metabolism,and provide a basis for the treatment of atherosclerosis.

关 键 词：枳壳 水煎液 动脉粥样硬化 巨噬细胞泡沫化 代谢组学 

分 类 号：R285[医药卫生—中药学]