摘要
目的基于网络药理学探讨运脾益肾方治疗小儿疳证药理作用机制。方法(1)通过数据库分别筛选出运脾益肾方相关药物活性成分、基因靶点与小儿疳证相关基因,得到共同作用靶点;利用数据构建PPI网络,进行GO功能和KEGG通路富集分析。通过AutoDock软件将PPI结果与筛选出的关键靶点与药物活性成分进行分子对接。(2)制备幼龄大鼠疳证模型,中药灌胃干预10 d,采集腓肠肌,实时荧光定量PCR法检测胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子受体-1(IGF-1R)、磷酸肌醇3-激酶(PI3K)、蛋白激酶B(AKT)、哺乳动物雷帕霉素靶蛋白(mTOR)的mRNA相对表达量。结果(1)共得出运脾益肾方386个药物活性成分及小儿疳证957个靶点基因,共同作用靶点174个。运脾益肾方可能通过调控缺氧诱导因子-1(HIF-1)、PI3K/AKT/mTOR等信号通路,主要作用于白蛋白(ALB)、白介素-6(IL-6)、缺氧诱导因子-1α(HIF-1α)、IGF-1R、mTOR等关键靶点,参与蛋白质代谢、氧代谢、糖代谢等过程。(2)与正常组相比,模型组大鼠腓肠肌组织中IGF-1、IGF-1R、PI3K、AKT、mTOR的mRNA的表达量显著降低(P<0.05);而运脾益肾方(YP)组及运脾益肾方+高蛋白饲料(YH)组中这些因子的表达量显著上调(P<0.05),且YH组改善效果优于YP组。结论运脾益肾方具有多成分、多靶点的特点,且能够调控疳证大鼠PI3K/AKT/mTOR信号通路上相关靶点,这可能是其治疗疳证的作用机制与靶点之一。
Objective To investigate the pharmacological mechanisms of the Yunpi Yishen in the treatment of infantile malnutrition syndrome by using network pharmacology methods.Methods(1)Active compounds of Yunpi Yishen Decoction and gene targets related to infantile malnutrition syndrome were screened from various databases.A protein-protein interaction(PPI)network was constructed using the data,and Gene Ontology(GO)functional enrichment and KECG pathway analysis were performed.Key targets and active pharmaceutical components were docked with the PPI results and literature reviews by using AutoDock software.(2)After established the rat model of infantile malnutrition,The YP and YH groups received the herbal formula via gavage for 10 days.Subsequently,the gastrocnemius muscle was collected from the rats,and the relative expression levels of mRNA for IGF-1,IGF-1R,PI3K,AKT,and mTOR were measured using qRT-PCR.Results(1)A total of 386 active compounds from Yunpi Yishen Formula and 957 target genes related to infantile malnutrition syndrome were identified.Analysis revealed 174 common action targets.Network results indicated that Yunpi Yishen Formula may exert its effects by modulating signaling pathways such as HIF-1,AGE-RAGE,and PI3K/AKT-mTOR,targeting key proteins like ALB,IL-6,HIF-1α,IGF-1R,and mTOR.These interactions are to influence processes such as protein metabolism,oxygen metabolism,and glucose metabolism.(2)The mRNA levels of IGF-1,IGF-1R,PI3K,AKT,and mTOR in the gastrocnemius muscle tissues of rats were ex-pressed.The model group showed lower levels than those of the normal group(P<0.05).After treatment with Yunpi Yishen formula,the mRNA expression levels of IGF-1,IGF-1R,PI3K,AKT,and mTOR in YP and YH groups increased significantly(P<0.05),and the YH group showed better results than those of the YP group(P<0.05).Conclusion Yunpi Yishen Formula may work by using active ingredients like quercetin,ethyl acetate of orange blossom,oleoresin,and baicalein to target on the key pathways such as ALB,IL-6,HIF-lα,IGF-1R,and mTOR.The experiments have shown that it can upregulate relevant targets in the PI3K/AKT/mTOR signaling pathway in the gastrocnemius muscle tissue of rats with nutritional disorders,which may be one of the mechanisms and targets for exerting its therapeutic effects.
作者
黄敬
彭玉
庞平
吴昊
唐鑫
江雪
陈颖钰
叶倩
徐平健
HUANG Jing;PENG Yu;PANG Ping;WU Hao;TANG Xin;JIANG Xue;CHEN Yingyu;YE Qian;XU Pingjian(Guizhou University of Traditional Chinese Medicine,Guiyang 550025,Guizhou,China;The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550003,Guizhou,China;Tongren Traditional Chinese Medicine Hospital,Tongren 554300,Guizhou,China;Yuanshen Rehabilitation Hospital,Xiamen 361021,Fujian,China;People's Hospital of Tongren,Tongren 554300,Guizhou,China)
出处
《贵州中医药大学学报》
2025年第3期80-89,共10页
Journal of Guizhou University of Traditional Chinese Medicine
基金
国家中医药管理局项目(国中医药人教函[2022]75)
贵州省中医药管理局项目(QZYY-2025-045)
贵州中医药大学校内项目(贵中医大创合字[2024]40)。
关键词
小儿疳证
运脾益肾方
网络药理学
PI3K/AKT/mTOR通路
作用机制
蛋白质代谢
children infantile malnutrition syndrome
Yunpi Yishen Formula
network pharmacology
PI3K/AKT/mTOR signaling pathway
mechanism of action
protein metabolism
