蒙药嘎拉图呼和调控肿瘤微环境抗胃癌作用机制研究  

Study on the Mechanism of Mongolian Medicine Galatu Huhe in Regulating the Tumor Microenvironment Against Gastric Cancer

作　　者：刘静 李明钦 王梓瑄 张谦 李君 张微 王芳 王跃武 LIU Jing;LI Mingqin;WANG Zixuan;ZHANG Qian;LI Jun;ZHANG Wei;WANG Fang;WANG Yuewu(College of Pharmacy,Inner Mongolia Medical University,Hohhot 010110 Inner Mongolia,China;College of Basic Medicine,Inner Mongolia Medical University,Hohhot 010110 Inner Mongolia,China)

机构地区：[1]内蒙古医科大学药学院,内蒙古呼和浩特010110 [2]内蒙古医科大学基础医学院,内蒙古呼和浩特010110

出　　处：《中药新药与临床药理》2025年第2期182-196,共15页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：内蒙古自治区自然科学基金项目(2023QN08050);内蒙古自治区高等学校科学研究项目(NJZY23135)。

摘　　要：目的揭示蒙药复方嘎拉图呼和(GLTHH)治疗胃癌(gastric cancer)的潜在靶点及调控网络,为GLTHH的深入研究与临床应用提供重要的数据支持,为蒙药治疗胃癌提供新的研究视角。方法采用HPLC-Q-Exactive MS技术对GLTHH的化学成分进行快速准确的分析和鉴定,明确其潜在药效化学成分群,并解析其裂解规律;基于质谱信息在TCMSP数据库筛选活性化学成分,利用Pharm Mapper数据库探寻其潜在作用靶点;基于GEO数据库收集人类胃癌组织与正常组织数据进行差异基因筛选与免疫细胞浸润分析,获得疾病基因以及与疾病相关免疫细胞;将疾病基因与GLTHH潜在作用靶点取交集,获得治疗关键靶点,关键靶点进行免疫细胞相关性分析,确定最终治疗的核心靶点,并采用分子对接验证结合能力。结果GLTHH中共鉴定出105个化合物,利用数据库获得658个潜在作用靶点;GEO数据经矫正后获得206个DEGs,与GLTHH潜在作用靶点取交集后得到8个关键靶点基因。免疫浸润分析发现与正常组相比,胃癌组NK细胞(自然杀伤细胞)显著性降低,关键靶点基因中15-羟基前列腺素脱氢酶(HPGD)与NK细胞正相关,转谷氨酰胺酶2(TGM2)与NK细胞负相关。结论GLTHH可能通过调节肿瘤微环境,阻断胃癌细胞所诱导的NK细胞免疫抑制作用,从而达到治疗目的。Objective To reveal the potential targets and regulatory networks of the Mongolian medicine Galatu Huhe(GLTHH)in the treatment of gastric cancer,and to provide important data support for the in-depth research and clinical application of GLTHH and offer a new research perspective for Mongolian medicine in the treatment of gastric cancer.Methods HPLC-Q-Exactive MS was used to rapidly and accurately analyze and identify the chemical components of GLTHH,as well as to determine its potential pharmacological chemical component groups and elucidate their fragmentation patterns.Active chemical components were screened using the TCMSP database based on mass spectrometry data.Their potential targets were identified using the Pharm Mapper database.The data of human gastric cancer and normal tissue were collected from the GEO database for differential gene screening and immune cell infiltration analysis to obtain disease-related genes and immune cells.The intersection of disease genes and potential targets of GLTHH was taken to obtain key therapeutic targets,which were then analyzed for their correlation with immune cells to identify core therapeutic targets.Finally,molecular docking was employed to verify binding capabilities.Results A total of 105 compounds were identified in GLTHH,and 658 potential targets were obtained.After correction of GEO data,206 differentially expressed genes(DEGs)were identified.The intersection of DEGs with the potential targets of GLTHH yielded eight key target genes.Immune infiltration analysis showed that,compared with the normal group,NK cells were significantly decreased in the gastric cancer group.Among the key target genes,15-hydroxyprostaglandin dehydrogenase(HPGD)was positively correlated with NK cells,while transglutaminase 2(TGM2)was negatively correlated with NK cells.Conclusion GLTHH may achieve therapeutic effects by regulating the tumor microenvironment and blocking immunosuppressive effect of NK cells induced by gastric cancer cells.

关 键 词：蒙药 嘎拉图呼和 胃癌 HPLC-Q-Exactive MS 免疫逃逸 肿瘤微环境 

分 类 号：R285.5[医药卫生—中药学]