摘要
目的基于网络药理学及动物实验探讨芜菁改善肺纤维化(PF)的活性成分、关键靶点及作用机制。方法通过中药系统药理数据库与分析平台数据库筛选芜菁活性成分及作用靶点,联合在线人类孟德尔遗传数据库(OMIM)、药物数据库(DrugBank)等疾病数据库获取PF相关靶点,取交集后构建蛋白-蛋白互作(PPI)网络筛选核心靶点,并开展基因本体论(GO)/京都基因和基因组百科全书(KEGG)通路富集分析。动物实验采用博来霉素(BLM)诱导PF小鼠模型,通过HE和Masson染色评估肺组织病理变化,qRT-PCR检测肿瘤坏死因子α(TNF-α)、磷脂酰肌醇3激酶(PI3K)、丝氨酸/苏氨酸蛋白激酶1(AKT1)mRNA表达,免疫荧光染色检测TNF-α、PI3K、AKT1蛋白表达。结果芜菁中鉴定出的68种活性成分可能通过作用于TNF-α、AKT1等89个潜在靶点,调控PI3K-Akt等信号通路。动物实验结果显示,芜菁多糖(BRPs)可显著减轻BLM诱导的小鼠PF程度;肺组织HE和Masson染色表明,与BLM组相比,BLM+BRPs组肺泡结构破坏减轻,炎症细胞浸润明显减少,胶原纤维沉积显著下降。进一步机制研究表明,BRPs能够显著下调PF小鼠肺组织中TNF-α、PI3K、AKT1的mRNA和蛋白表达水平。结论芜菁通过“多成分-多靶点-多通路”的方式协同改善PF;BRPs是芜菁主要活性成分之一,并通过抑制TNF-α/PI3K-Akt信号通路发挥抗PF作用。
Objective To explore the active components,key targets,and mechanism of action of turnip in alleviating pulmonary fibrosis(PF)based on network pharmacology and animal experiments.Methods The active components and targets of Brassica rapa L.were screened using the traditional Chinese medicine systems pharmacology database and analysis platform database,and PF-related targets were obtained from disease databases such as online mendelian inheritance of man(OMIM)and DrugBank.The intersection targets were used to construct a protein-protein interaction(PPI)network to identify core targets,followed by gene oncology(GO)/Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.In the animal experiments,a bleomycin-induced PF mouse model was established.Pathological changes in lung tissue were evaluated using HE and Masson staining.qRT-PCR was used to detect the mRNA expression of tumor necrosis factor-α(TNF-α),phosphatidylinositol 3-kinase(PI3K),and akstrain transforming 1(AKT1),and immunofluorescence staining was used to measure the protein expression of TNF-α,PI3K,and AKT1.Results The 68 active components identified in Brassica rapa L.may regulate PI3K-Akt signaling pathway by acting on 89 potential targets such as TNF-αand AKT1.The results of animal experiments showed that polysaccharide of Brassica rapa L.(BRPs)could significantly reduce the degree of bleomycin induced pulmonary fibrosis in mice;HE and Masson staining of lung tissue showed that compared with the model group,the damage of alveolar structure,the infiltration of inflammatory cells and the deposition of collagen fibers in the BRPs treatment group were significantly reduced.Further mechanism studies showed that BRPs could significantly down-regulate the mRNA and protein expression levels of TNF-α,PI3K and AKT1 in lung tissue of pulmonary fibrosis mice.Conclusion Brassica rapa L.can synergistically alleviate pulmonary fibrosis through“multi-component,multi-target and multi-channel”approach;BRPs is one of the main active components,and plays an anti-fibrosis role by inhibiting TNF-α/PI3K Akt signaling pathway.
作者
孙铭雨
刘桂花
郭君婷
程爱斌
辛婧
苗庆芳
高瑞娟
门秀丽
Sun Mingyu;Liu Guihua;Guo Junting;Cheng Aibin;Xin Jing;Miao Qingfang;Gao Ruijuan;Men Xiuli(Key Laboratory of Chronic Diseases,School of Basic Medical Sciences,North China University of Science and Technology,Tangshan 063210;NHC Key Laboratory of Biotechnology for Microbial Drugs,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050;Food Testing Research Laboratory,Xinjiang Uygur Autonomous Region Institute of Materia Medica,Urumqi 830000;Intensive Care Unit,North China University of Science and Technology Affiliated Hospital,Tangshan 063210)
出处
《安徽医科大学学报》
北大核心
2025年第12期2227-2234,共8页
Acta Universitatis Medicinalis Anhui
基金
中国医学科学院医学与健康科技创新工程项目(编号:2021-I2M-1-026)
新疆维吾尔自治区自然科学基金项目(编号:2024D01A120)。
关键词
芜菁
芜菁多糖
肺纤维化
网络药理学
肿瘤坏死因子-Α
PI3K-AKT信号通路
TNF-α信号通路
Brassica rapa L.
polysaccharide of Brassica rapa L.
pulmonary fibrosis
network pharmacology
tumor necrosis factor-α
PI3K-Akt signaling pathway
TNF-αsignaling pathway
