基于血清化学成分研究藏药六味木香丸治疗慢性非萎缩性胃炎的分子作用机制  

Molecular Mechanism of Tibetan Medicine Liuwei Muxiang Pills for Treating Chronic Non Atrophic Gastritis Based on Serum Active Chemical Components

作　　者：仁青东主[1] 冯学梅 洛桑东智[1] 华青措 三智加[1] Renqing-Dongzhu;FENG Xuemei;Luosang-Dongzhi;HUA Qingcuo;SAN Zhijia(Tibetan Medical College,Qinghai University,Xining 810001,China;Qinghai Provincial Tibetan Hospital,Xining 810007,China)

机构地区：[1]青海大学藏医学院,西宁810001 [2]青海省藏医院,西宁810007

出　　处：《高原科学研究》2023年第3期58-70,共13页Plateau Science Research

基　　金：青海省科技厅应用基础研究项目(2018-ZJ-732);国家科学技术部国家重点研发计划(2017YFC1703902)。

摘　　要：目的:以小鼠实验入血化学成分研究六味木香丸治疗慢性非萎缩性胃炎的作用靶点与机制。方法:采用Thermo TSQ-MS检测六味木香丸8种入血成分的含量;网络药理学方法(Swiss Target Prediction、Herb、GeneCards、OMIM、Cytoscape、STRING)筛选入血成分及疾病靶点,绘制交集靶点维恩图,构建“入血成分-靶点”及PPI关系网络;生物信息学方法(GO、KEGG)分析生物过程、信号通路,挖掘网络药理学预测靶点与动物实验差异表达蛋白(干预1、2个月)交集靶点,并使用Mestro进行分子对接;最后,通过Western Blot(WB)实验在动物组织验证共同交集靶点。结果:MRM靶向检测8个入血成分质谱响应良好,线性方程的R2接近于1,满足物质靶向检测与定量要求;六味木香丸8种入血成分映射416个靶点,慢性非萎缩性胃炎疾病靶点1250个,入血成分和疾病共同交集靶点157个。GO结果显示,入血成分的靶蛋白主要富集到基因表达的正调节、凋亡过程的负调控和炎症反应等生物过程,功能蛋白质与酶以及ATP结合,KEGG结果显示涉及有PI3K-Akt、MAPK、IL-17、TNF等信号通路;网络药理学预测靶点与小鼠模型蛋白库比较显示,共同交集靶点有TFAM、PARP1、COL3A1、NQO1、IDO1、CTSL、HMGCR等。分子对接结果发现,8个入血成分与3个核心蛋白受体对接分数均低于-5.0 kJ/mol。WB结果显示,3个靶蛋白在模型组、对照组中具有高表达,干预组的低、中、高剂量中均具有下调作用。结论:六味木香丸入血成分对治疗慢性非萎缩性胃炎具有潜在的抗炎、抗炎癌转化的作用。Objective To explore the target and mechanism of Tibetan medicine Liuwei Muxiang(LWMX)Pills in the treatment of chronic non-atrophic gastritis through the chemical composition of mouse serum.Methods Thermo TSQ-MS were used to detect the main chemical components of the Tibetan medicine LWMX Pills in vivo.The blood components of the mouse model were targeted and assayed.After selecting eight blood components,the common targets were obtained in the Swiss Target Prediction and Herb database,and the duplicate targets were removed and the names of related genes were corrected.Use Gene Cards and OMIM disease database to obtain the disease target of chronic non-atrophic gastritis,optimize the final target of the disease,and construct the Venn map from the target of blood components and the disease target.The"drug-serum chemical component-target"network was built using Cytascape software,and the STRING data platform predicted the protein protein interaction relationship,and the PPI network was built.DAVID database was used to conduct GO enrichment analysis and KEGG pathway analysis on the intersection target.Compare the network pharmacology prediction target with the deferentially expressed protein in the mouse model Gastric mucosa(1 and 2 month protein libraries),screen common intersection targets,STRING builds the PPI network again,and uses Autodock and Python to achieve Macromolecular docking;Finally,validation experiments were conducted using Western Blot(WB)experiment on common intersection targets in animal tissues.Results It was found that eight serum chemical components of the Tibetan medicine Liuwei Muxiang Pill mapped 416 targets,1250 targets of chronic non Atrophic gastritis related diseases,and 157 intersection targets were obtained by intersection of component targets and disease targets.The GO analysis results show that the target proteins related to the active ingredients of Liuwei Muxiang Pills are mainly enriched in biological processes such as positive regulation of gene expression,negative regulation of

关 键 词：血清化学成分 藏药六味木香丸 慢性非萎缩性胃炎 分子作用机制 

分 类 号：R29[医药卫生—民族医学]