基于UPLC-Q-Orbitrap HRMS结合网络药理学探讨半夏泻心汤入血成分及治疗脾虚型溃疡性结肠炎的作用机制  

Blood-absorbed components of Banxia Xiexin Tang and the mechanism of its therapeutic effect on spleen deficiency type ulcerative colitis based on UPLC-Q-Orbitrap HRMS and network pharmacology

作　　者：朱海燕 杨福权 左秦川 房智彦 黄丽莉 淮文英 王艳秋 张天娥[1] ZHU Hai-yan;YANG Fu-quan;ZUO Qin-chuan;FANG Zhi-yan;HUANG Li-li;HUAI Wen-ying;WANG Yan-qiu;ZHANG Tian-e(School of Basic Medicine,Chengdu University of TCM,Chengdu 611137,China;Guangyuan Hospital of Traditional Chinese Medicine,Guangyuan 628000,China;Pujiang County(Sichuan)Hospital of Traditional Chinese Medicine,Pujiang 611630,China;Guangzhou University of Traditional Chinese Medicine Shenzhen Hospital(Futian),Shenzhen 518034,China;Research Center of Traditional Chinese Medicine and Stem Cell,Chengdu 611137,China)

机构地区：[1]成都中医药大学基础医学院,成都611137 [2]广元市中医医院,广元628000 [3]蒲江县中医医院,蒲江611630 [4]广州中医药大学深圳医院(福田),深圳518034 [5]中医药和干细胞研究中心,成都611137

出　　处：《天然产物研究与开发》2024年第9期1610-1624,共15页Natural Product Research and Development

基　　金：四川省科技厅项目(2023YFS0333,2022NSFSC1549);成都中医药大学青基进阶人才专项建设项目(2023)。

摘　　要：研究通过建立脾虚型溃疡性结肠炎(ulcerative colitis,UC)模型,采用液相芯片对大鼠血清中炎性细胞因子进行高通量检测,同时以HE染色对结肠组织进行炎症分级评分,验证半夏泻心汤(Banxia Xiexin Tang,BXT)对脾虚型UC的药理作用。随后利用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱(UPLC-Q-Orbitrap HRMS)对BXT入血成分进行分析,并结合网络药理学,探究BXT治疗脾虚型UC的作用机制。结果显示,UC能够增加大鼠血清中细胞因子白细胞介素-1α(interleukin-1α,IL-1α)、白细胞介素-10(interleukin-10,IL-10)、白细胞介素-18(interleukin-18,IL-18)、干扰素-γ(interferon-γ,IFN-γ)、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)表达水平;BXT可降低血清炎性细胞因子含量,且BXT高剂量组(20 g/kg)下降最明显,无明显炎细胞浸润,表明BXT对脾虚型UC具有一定的治疗作用。大鼠血清中发现入血成分共20个;网络药理学筛选出BXT治疗UC相关靶点87个,涉及炎症反应、炎症反应调节、微生物反应等生物过程,参与了IL-17、脂质与动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路、TNF等信号通路。综上可知,BXT治疗脾虚型UC可能与抑制肠道炎症、调节肠道微生物及保护肠道屏障等多个途径相关,从而达到治疗UC效果。This experiment first established a model of spleen deficiency type ulcerative colitis(UC),and then used high-throughput liquid chip technology to detect inflammatory cytokines in rat serum.HE staining was used to grade inflammation in colon tissue.All of the above are used to verify the pharmacological effect of Banxia Xiexin Tang(BXT)on spleen deficiency type colitis.Secondly,UPLC-Q-Orbitrap HRMS was used to analyze the components of BXT in rat blood,combined with network pharmacology,to explore the mechanism of action of BXT in treating UC of spleen deficiency type.The results showed that UC could increase the level of inflammatory factors interleukin-1α(IL-1α),interleukin-10(IL-10),interleukin-18(IL-18),interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α)in rat serum;BXT can decrease the content of serum inflammatory factor,and the effect of BXT high dose group(20 g/kg)was the most obvious,with no obvious infiltration of inflammatory cells.it is suggested that BXT has a certain therapeutic effect on UC with spleen deficiency.A total of 20 components were found in rat serum.On this basis,network pharmacological research has screened 87 targets targets related to BXT in the treatment of UC,involving inflammatory response,inflammatory response regulation,microbial response and other biological processes,participating in the IL-17 signaling pathway,Lipid and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications and TNF signaling pathway.The results suggest that the treatment of spleen deficiency type UC with BXT may be related to the inhibition of intestinal inflammation,the regulation of intestinal microbes and the protection of intestinal barrier,so as to achieve the therapeytic effect of UC.

关 键 词：半夏泻心汤 脾虚型溃疡性结肠炎 UPLC-Q-Orbitrap HRMS 入血成分 网络药理学 作用机制 

分 类 号：R285.5[医药卫生—中药学]