目的:用无水乙醇诱导大鼠胃损伤模型,验证特殊膳食和渭肽的胃保护效果,并结合网络药理学筛选相关通路靶点,为临床应用提供了实验依据。方法:选用雄性SD大鼠预防性给药,分别给予不同剂量和渭肽及阳性药雷尼替丁,给药结束后除正常对照组外均用无水乙醇造模1h,采用腹主动脉采血并取胃组织,肉眼观察及HE、PAS染色镜下观察胃壁形态特点,检测血清中白细胞介素6(IL-6)和过氧化氢酶(CAT)的表达情况。通过TCMSP和HERB数据库获取和渭肽中各药物的化学成分,在GeneCards和OMIM数据库中搜索相关作用靶点绘制Venn图;通过STRING网站、Cytoscape3.9.1软件和DAVID平台绘制PPI网络图并进行GO及KEGG富集分析;运用CytoScape3.9.1软件构建和渭肽药物-活性成分-疾病-靶点网络图,预测和渭肽发挥胃保护作用的核心靶点及主要活性成分。结果:动物实验相关生理生化指标及HE、PAS染色结果表明,特殊膳食和渭肽对无水乙醇诱导的大鼠急性胃损伤具有保护作用。网络药理学结果表明,和渭肽可能通过作用于TP53、EGFR、AKT1等核心靶点,调节PI3K-Akt、MAPK等炎症信号通路发挥预防胃损伤的作用。结论:和渭肽通过调节炎症因子水平、减轻氧化应激、维持胃黏液屏障的完整性、调节PI3K-Akt、MAPK等炎症信号通路发挥预防胃损伤的作用。

Objective: In this study, the gastric injury model of rats induced by anhydrous ethanol was used to verify the gastric protective effect of special dietary Hewei peptide, and the related pathway targets were screened by network pharmacology, which provided experimental basis for clinical application. Methods: Male SD rats were selected for preventive administration, and different doses of Hewei peptide and positive drug ranitidine were given respectively. After the administration, except for the normal control group, anhydrous ethanol was used to establish the model for 1 h. Abdominal aortic blood was collected and gastric tissue was taken. The morphological characteristics of gastric wall were observed by naked eye and HE and PAS staining, and the expression of interleukin-6 ( IL-6 ) and catalase ( CAT ) in serum was detected. The chemical constituents of each drug in Hewei peptide were obtained from TCMSP and HERB databases, and Venn diagram was drawn by searching for relevant targets in GeneCards and OMIM databases. PPI network diagram was drawn by STRING website, Cytoscape3.9.1 software and DAVID platform, and GO and KEGG enrichment analysis was carried out. CytoScape 3.9.1 software was used to construct the drug-active component-disease-target network diagram of Hewei peptide, and to predict the core targets and main active components of Hewei peptide for gastric protection. Results: The results of physiological and biochemical indexes and HE and PAS staining in animal experiments showed that special diet and Weitai peptide had protective effects on acute gastric injury induced by anhydrous ethanol in rats. The results of network pharmacology showed that Hewei peptide may play a role in preventing gastric injury by acting on core targets such as TP53, EGFR and AKT1, and regulating inflammatory signals such as PI3K-Akt and MAPK. Conclusion: Hewei peptide plays a role in preventing gastric injury by regulating the level of inflammatory factors, reducing oxidative stress, maintaining the integrity of gastric mucus barrier, and regulating PI3K-Akt, MAPK and other inflammatory signaling pathways.