中药药理与临床2025，Vol.41Issue(5)：43-49,7.
三七总皂苷对阿司匹林致斑马鱼肠道损伤的保护作用及机制
Protective Effect and Mechanism of Panax notoginseng Saponins on Aspirin-Induced Intestinal Injury in Zebrafish
摘要
Abstract
Objective:To investigate the protective effect and mechanism of Panax notoginseng saponins(PNS)on aspirin-induced intestinal injury in zebrafish based on the zebrafish model and network pharmacology.Methods:Zebrafish intestinal injury was induced by aspirin,and the effect of PNS on intestinal phagocytosis,goblet cell secretion,and neutrophil aggregation was evaluated using neutral red staining,Alcian blue staining,and changes in neutrophil cell counts,respectively.ELISA was used to detect the expression levels of tumor necrosis factor-α(TNF-α),prostaglandin E2(PGE2),and tight junction proteins ZO-1 and occludin in zebrafish intestines.Network pharmacology was employed to predict the potential mechanism of PNS in intervening in intestinal injury,and the expression of related target genes was verified by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results:Compared with the model group,PNS significantly increased the neutral red staining area in the intestines of zebrafish(P<0.01)to improve intestinal phagocytic function,increased the Alcian blue staining area(P<0.01)to enhance goblet cell secretion,reduced the number of neutrophils in the intestine(P<0.01)to improve the degree of intes-tinal injury,and decreased the content of TNF-α and PGE2 in the intestines of zebrafish to increase the secretion of ZO-1 and occludin,thus repairing the damaged intestinal mucosal barrier.Network pharmacological analysis identified 297 potential targets for PNS,1 797 targets for intestinal injury,and 128 potential targets for PNS intervention in intestinal injury.The top five ranked targets by degree value in the protein-protein interaction(PPI)network analysis were AKT serine/threonine kinase 1(AKT1),epidermal growth factor receptor(EGFR),signal transducer and activator of transcription 3(STAT3),heat shock protein 90 alpha family class A member 1(HSP90AA1),and mitogen-acti-vated protein kinase 3(MAPK3).Gene Ontology(GO)analysis revealed that the biological processes primarily included phosphorylation,response to hormones,cell activation,and response to xenobiotic stimuli;cellular components involved receptor complexes,membrane rafts,ex-tracellular matrix,and endosomal lumen;molecular functions focused on protein kinase activity,kinase binding,phosphatase binding,and nu-clear receptor activity.Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis indicated that PNS treatment of intestinal injury mainly involved cancer pathways,the PI3K-Akt signaling pathway,chemical carcinogenesis-receptor activation,T cell receptor signaling pathway,and MAPK signaling pathway.RT-qPCR results showed that PNS inhibited the gene expression of Keap1,Akt1,Akt2,and Mapk1 while increasing the expression of Nrf2,Ho-1,and Egfr.Conclusion:PNS exhibits a beneficial therapeutic effect on aspirin-induced intestinal injury in ze-brafish,and its protective mechanism may be related to the regulation of the KEAP1/Nrf2,PI3K-Akt,and MAPK signaling pathways.关键词
三七总皂苷/阿司匹林/肠道损伤/斑马鱼/分子机制/丝氨酸/苏氨酸激酶1/表皮生长因子受体/信号传导及转录激活因子3/热休克蛋白90AA1/丝裂原活化蛋白激酶3Key words
Panax notoginseng saponins/Aspirin/Intestinal injury/Zebrafish/Molecular mechanism/AKT1/EGFR/STAT3/HSP90AA1/MAPK3引用本文复制引用
黄英红,郭慧琼,黄海丽,覃其静,赵崇军,肖特,孙宗喜..三七总皂苷对阿司匹林致斑马鱼肠道损伤的保护作用及机制[J].中药药理与临床,2025,41(5):43-49,7.基金项目
广西科技基地和人才专项(桂科AD22035058) （桂科AD22035058）
全国中药特色技术传承人才培训项目(国中医药人教函[2023]96号) （国中医药人教函[2023]96号）
广西国际壮医医院高层次人才队伍建设三年行动计划项目(编号:GZCX20231204) （编号:GZCX20231204）
全国名中医黄汉儒学术思想及临床经验传承推广中心(编号:2022V004). （编号:2022V004）
