中医药学报2024，Vol.52Issue(1)：49-57,9.DOI:10.19664/j.cnki.1002-2392.240010
基于网络药理学和实验验证的六君子汤治疗慢性萎缩性胃炎的作用机制研究
Mechanism of Six Gentlemen Decoction in Treating Chronic Atrophic Gastritis Based on Network Pharmacology and Experimental Verification
摘要
Abstract
Objective:To predict the potential molecular mechanism of six gentlemen decoction in the treatment of chronic atrophic gastritis(CAG)by network pharmacological method,and to verify its efficacy and mechanism in combination with animal experiments.Methods:The active components and drug targets of six gentlemen decoction were collected in TCMSP database;the relevant targets of CAG are filtered through databases PharmGkb,OMIM,GeneCards and DrugBank.The common target is obtained by intersection of drug target and disease target.The active ingredient intersection target network diagram is made by using the software Cytoscape 3.8.0,and the enrichment analysis of GO and KEGG is carried out by using R software.The rat model of chronic atrophic gastritis(CAG)was established by compound factor modeling method.The model was evaluated 16 weeks after modeling,and then the rats were intervened with six gentlemen decoction for 4 weeks.The pathological changes of rat gastric mucosa were observed,and the levels of interleukin-1β(IL-1β)and interleukin-6(IL-6)in serum of rats were detected by enzyme-linked immunoassay.The expression levels of Janus kinase 1(JAK1),Signal transducer and activator of transcription3(STAT3),P53,and B-cell lymphoma-2(BCL-2)were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction to verify the effect of six gentlemen decoction on CAG.Results:125 active ingredients,241 potential targets,377 CAG targets,48 intersection targets were screened out,and the key targets involved IL-1 β,IL-6,TP53,BCL-2,etc.The KEGG enrichment analysis shows that the treatment of CAG with six gentlemen decoction involves JAK/STAT,PI3K/Akt,HIF-1,IL-17 and other signal pathways.The experimental results showed that compared with the model group,the appearance and pathological morphology of gastric mucosa of rats in six gentlemen decoction group were improved,the content of IL-6 in serum of rats decreased(P<0.05),and IL-1 β content decreased significantly(P<0.01).The expression of JAK1,STAT3,and BCL-2 mRNA decreased(P<0.05)in gastric mucosa and P53 mRNA decreased significantly(P<0.01);JAK1,STAT3,P53 protein decreased significantly(P<0.01),and BCL-2 protein content decreased(P<0.05).Conclusion:Six gentlemen decoction can improve chronic atrophic gastritis,its mechanism may be through inhibiting IL-1β and IL-6.It can subsequently inhibit the expression of downstream JAK1/STAT3 signal pathway,and inhibit the expression of P53 and BCL-2 factors with the activation of this pathway,so as to effectively regulate the apoptosis of gastric mucosa cells and achieve the role of repairing the mucosa.关键词
六君子汤/慢性萎缩性胃炎/分子机制/实验验证/网络药理学Key words
Six gentlemen decoction/Chronic atrophic gastritis/Molecular mechanism/Experimental verification/Network pharmacology分类
医药卫生引用本文复制引用
罗文谦,涂文玲,洪银洁,陈梅妹,甘慧娟..基于网络药理学和实验验证的六君子汤治疗慢性萎缩性胃炎的作用机制研究[J].中医药学报,2024,52(1):49-57,9.基金项目
国家自然科学基金项目(81873237) （81873237）
福建省自然科学基金项目(2021J01929) （2021J01929）
福建中医药大学校管课题(X2021010) （X2021010）
