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邵昌明,谢姗珊,智勇,曙阿克·哈尔恒,林柏桐,于燕艳,曾斌芳.基于网络药理学及实验验证探讨养阴活胃合剂治疗慢性萎缩性胃炎的作用机制[J].湖南中医药大学学报英文版,2023,43(5):847-856.[Click to copy
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| 基于网络药理学及实验验证探讨养阴活胃合剂治疗慢性萎缩性胃炎的作用机制 |
| 邵昌明,谢姗珊,智勇,曙阿克·哈尔恒,林柏桐,于燕艳,曾斌芳 |
| (新疆医科大学中医学院, 新疆 乌鲁木齐 830011;黑龙江中医药大学, 黑龙江 哈尔滨 150006) |
| 摘要: |
| 目的 基于网络药理学预测养阴活胃合剂治疗慢性萎缩性胃炎(chronic atrophic gastritis, CAG)的活性成分及潜在靶点,通过动物实验进行验证PI3K-Akt、信号通路,为临床应用提供科学依据。方法 通过中医药系统药理学数据库和分析平台(TCMSP)、SymMap数据库筛选得到中药的有效活性成分,同时从 GeneCard、OMIM和DisGeNET 数据库对CAG的靶点进行检索及筛选;预测其活性成分与疾病靶点,使用Cytoscape 3.7.1 软件构建网络图,对该网络进行拓扑分析筛选节点,利用STRING数据库分析核心靶点蛋白质-蛋白质相互作用(protein-protein interaction, PPI)网络,利用DAVID数据库对核心靶点基因进行GO和KEGG富集分析,探讨养阴活胃合剂治疗CAG的作用机制。实验验证:选用SPF级SD雄性大鼠,采用随机分配法分为空白组及造模组,利用N-甲基-N'-硝基-N-亚硝基胍(N-methyl-N'-nitro-N-nitrosoguanidine, MNNG)及饥饱失常法等方法进行造模,造模成功后随机分为模型组、维酶素组以及养阴活胃合剂低、中、高剂量组,每组10只,连续干预56 d;通过HE染色观察各组SD大鼠胃黏膜病理组织的变化,IHC检测各组大鼠胃黏膜PI3K、AKT1、mTOR中蛋白的表达含量。结果 从养阴活胃合剂中筛选出309个化学成分,涉及治疗CAG的靶点378个;筛选疾病靶点698个,共同靶点130个,根据节点自由度 ≥ 平均自由度,筛选核心靶点38个;通过GO、KEGG富集分析得到,养阴活胃合剂可以影响PI3K-Akt、TNF信号通路、MAPK信号通路、癌症相关等多个信号通路。养阴活胃合剂能够有效降低CAG模型大鼠胃组织中PI3K、AKT1、mTOR中蛋白表达情况(P<0.05)。结论 养阴活胃合剂通过多通路、多靶点治疗CAG,可以有效改善CAG模型大鼠胃黏膜细胞的增殖、凋亡及炎症反应等,有效调控PI3K/Akt信号通路,能够有效改善CAG大鼠胃黏膜的损伤。 |
| 关键词: 养阴活胃合剂 慢性萎缩性胃炎 胃黏膜 活性成分 网络药理学 作用机制 |
| DOI：10.3969/j.issn.1674-070X.2023.05.013 |
| Received:December 02, 2022 |
| 基金项目:新疆维吾尔自治区高校科研计划项目（XJEDU2021I018）；新疆维吾尔自治区区域协同创新专项（上海合作组织科技伙伴计划及国际科技合作计划）项目（2022E01008）。 |
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| Mechanism of action of Yangyin Huowei Mixture in treating chronic atrophic gastritis based on network pharmacology and experimental verification |
| SHAO Changming,XIE Shanshan,ZHI Yong,SHUAK Harheng,LIN Baitong,YU Yanyan,ZENG Binfang |
| (Xinjiang Medical University Institute of TCM, Urumqi, Xinjiang 830011, China;Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150006, China) |
| Abstract: |
| Objective To predict the active ingredients and potential targets of Yangyin Huowei Mixture (YYHWM) in treating chronic atrophic gastritis (CAG) based on network pharmacology, and to provide scientific basis for clinical application through animal experimental verification of PI3K-Akt, signaling pathways. Methods The effective active ingredients of Chinese medicine were screened by traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SymMap database, and the targets of CAG were searched and screened from GeneCard, OMIM and DisGeNET database. To predict the active ingredients and disease targets, the network diagram was constructed by Cytoscape 3.7.1 software and the nodes were screened by topological analysis of the network. The protein-protein interaction (PPI) network of the core target was analyzed by STRING database. GO and KEGG enrichment analysis was performed on the core target genes using DAVID database to explore the mechanism of YYHWM in treating CAG. Experimental verification: SPF SD male rats were selected and randomly divided into blank group and model group. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and hunger-satiety disorder were used for modeling. After successful modeling, they were randomly divided into model group, vitamycin group, low-, medium- and high-dose YYHWM groups, with 10 rats in each group, and were continuously intervened for 56 d. The pathological changes of gastric mucosa in SD rats were observed by HE staining. The expressions of PI3K, AKT1 and mTOR in gastric mucosa of rats in each group were determined by IHC. Results A total of 309 chemical ingredients were screened from YYHWM, involving 378 targets for treating CAG; a total of 698 disease targets and 130 common targets were screened, and 38 core targets were screened according to the the nodal degree of freedom ≥ average degree of freedom. Through GO and KEGG enrichment analysis, YYHWM can affect PI3K-Akt, TNF signaling pathway, MAPK signaling pathway, cancer-related and other signaling pathways. YYHWM can effectively reduce the protein expressions of PI3K, AKT1 and mTOR in gastric tissue of CAG model rats (P<0.05). Conclusion Through multi-pathway and multi-target treatment of CAG, YYHWM can effectively alleviate the proliferation, the apoptosis and inflammatory response of gastric mucosal cells in CAG model rats, and regulate PI3K/Akt signaling pathway, thus reducing gastric mucosal injury in CAG rats. |
| Key words: Yangyin Huowei Mixture chronic atrophic gastritis gastric mucosa active ingredients network pharmacology mechanism of action |
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