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基于网络药理学和多组学的冠玉止泻颗粒干预大鼠胃溃疡作用机制研究

Research on the mechanism of Guanyu Zhixie Granule in intervening gastric ulcers in rats based on network pharmacology and multi-omics.

作者信息

Ma Ting, Ji Peng, Wu Fan-Lin, Li Chen-Chen, Dong Jia-Qi, Yang Hao-Chi, Wei Yan-Ming, Hua Yong-Li

机构信息

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.

出版信息

Front Vet Sci. 2024 May 21;11:1390473. doi: 10.3389/fvets.2024.1390473. eCollection 2024.

DOI:10.3389/fvets.2024.1390473
PMID:38835897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11149358/
Abstract

OBJECTIVE

Guanyu Zhixie Granule (GYZXG) is a traditional Chinese medicine compound with definite efficacy in intervening in gastric ulcers (GUs). However, the effect mechanisms on GU are still unclear. This study aimed to explore its mechanism against GU based on amalgamated strategies.

METHODS

The comprehensive chemical characterization of the active compounds of GYZXG was conducted using UHPLC-Q/TOF-MS. Based on these results, key targets and action mechanisms were predicted through network pharmacology. GU was then induced in rats using anhydrous ethanol (1 mL/200 g). The intervention effects of GYZXG on GU were evaluated by measuring the inhibition rate of GU, conducting HE staining, and assessing the levels of , , , , Pepsin (), and epidermal growth factor (). Real-time quantitative PCR (RT-qPCR) was used to verify the mRNA levels of key targets and pathways. Metabolomics, combined with 16S rRNA sequencing, was used to investigate and confirm the action mechanism of GYZXG on GU. The correlation analysis between differential gut microbiota and differential metabolites was conducted using the spearman method.

RESULTS

For the first time, the results showed that nine active ingredients and sixteen targets were confirmed to intervene in GU when using GYZXG. Compared with the model group, GYZXG was found to increase the ulcer inhibition rate in the GYZXG-M group ( < 0.05), reduce the levels of , , in gastric tissue, and increase the levels of , , and . GYZXG could intervene in GU by regulating serum metabolites such as Glycocholic acid, Epinephrine, Ascorbic acid, and Linoleic acid, and by influencing bile secretion, the signaling pathway, and adipocyte catabolism. Additionally, GYZXG could intervene in GU by altering the gut microbiota diversity and modulating the relative abundance of , , , , and . The differential gut microbiota was strongly associated with serum differential metabolites. KEGG enrichment analysis indicated a significant role of the signaling pathway in GYZXG's intervention on GU. The changes in metabolites within metabolic pathways and the alterations in , , and mRNA levels in RT-qPCR experiments provide further confirmation of this result.

CONCLUSION

GYZXG can intervene in GU induced by anhydrous ethanol in rats by regulating gut microbiota and metabolic disorders, providing a theoretical basis for its use in GU intervention.

摘要

目的

冠宇止泻颗粒（GYZXG）是一种在干预胃溃疡（GU）方面疗效确切的中药复方。然而，其对GU的作用机制仍不清楚。本研究旨在基于整合策略探索其抗GU的机制。

方法

采用超高效液相色谱-四极杆/飞行时间质谱联用仪（UHPLC-Q/TOF-MS）对GYZXG的活性成分进行全面化学表征。基于这些结果，通过网络药理学预测关键靶点和作用机制。然后用无水乙醇（1 mL/200 g）诱导大鼠发生GU。通过测量GU抑制率、进行苏木精-伊红（HE）染色以及评估[具体物质1]、[具体物质2]、[具体物质3]、[具体物质4]、胃蛋白酶（Pepsin）和表皮生长因子（epidermal growth factor）的水平来评价GYZXG对GU的干预效果。采用实时定量聚合酶链反应（RT-qPCR）验证关键靶点和通路的mRNA水平。代谢组学结合16S核糖体RNA测序用于研究和确证GYZXG对GU的作用机制。采用斯皮尔曼方法进行差异肠道微生物群与差异代谢物之间的相关性分析。

结果

首次表明，使用GYZXG时，确认有9种活性成分和16个靶点参与干预GU。与模型组相比，发现GYZXG-M组的溃疡抑制率增加（P<0.05），胃组织中[具体物质1]、[具体物质2]、[具体物质3]水平降低，[具体物质4]、[具体物质5]、[具体物质6]水平升高。GYZXG可通过调节血清代谢物如甘氨胆酸、肾上腺素、抗坏血酸和亚油酸，并通过影响胆汁分泌、[具体信号通路]信号通路和脂肪细胞分解代谢来干预GU。此外，GYZXG可通过改变肠道微生物群多样性和调节[具体微生物1]、[具体微生物2]、[具体微生物3]、[具体微生物4]、[具体微生物5]的相对丰度来干预GU。差异肠道微生物群与血清差异代谢物密切相关。京都基因与基因组百科全书（KEGG）富集分析表明[具体信号通路]信号通路在GYZXG对GU的干预中起重要作用。代谢途径内代谢物的变化以及RT-qPCR实验中[具体物质1]、[具体物质2]、[具体物质3] mRNA水平的变化进一步证实了这一结果。

结论

GYZXG可通过调节肠道微生物群和代谢紊乱来干预大鼠无水乙醇诱导的GU，为其在GU干预中的应用提供了理论依据。

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