巴蜀颗粒治疗气道炎症的作用机制研究  

Study on the mechanism of Bashu Granule in treating airway inflammation

作　　者：古丽再帕尔·托合尼亚孜 陈伟 王楠 马芹 GVLZAPAR Tohniyaz;CHEN Wei;WANG Nan;MA Qin(School of Pharmacy,Xinjiang Medical University,Urumqi 830011,China;Xinjiang Huashidan Pharmaceutical Research Co.,Ltd,Urumqi 830011,China)

机构地区：[1]新疆医科大学药学院,新疆乌鲁木齐830011 [2]新疆华世丹药物研究有限责任公司,新疆乌鲁木齐830011

出　　处：《云南民族大学学报（自然科学版）》2024年第4期455-463,共9页Journal of Yunnan Minzu University:Natural Sciences Edition

基　　金：新疆维吾尔自治区十四五重大科技专项(2022A03017-2);新疆公共卫生关键技术研发与防疫体系建设专项(2020A03004-2).

摘　　要：采用网络药理学、分子对接和细胞炎症模型方法,研究巴蜀颗粒治疗气道炎症的作用靶点和机制.通过TCMSP和GeneCard等数据库对巴蜀颗粒中药材成分和靶点,气道炎症相关靶点进行搜集;采用富集分析对相关靶点进行生物生理过程分析,通路分析;采用pymol软件将筛选出来的潜在活性成分与核心蛋白靶点进行分子对接.建立细菌脂多糖(LPS)诱导巨噬细胞炎症模型,用Western-blot法检测巴蜀颗粒及不同活性成分对iNOS和p65等蛋白表达量的影响.网络药理学结果显示巴蜀颗粒治疗气道炎症的药效成分有8个,作用靶点有9个;GO富集分析得到1368个生理过程;KEGG富集得到134条相关信号通路;蛋白分子模拟对接发现槲皮素、山奈酚和木犀草素等成分与AKT1、MAPKs的结合能比较低,为优秀结合位构象.细胞实验结果显示巴蜀颗粒组对比LPS刺激组可降低iNOS蛋白的表达量,明显抑制p65蛋白磷酸化.预测出的潜在活性成分也可以不同程度降低iNOS表达量.巴蜀颗粒可能通过槲皮素、山奈酚、木犀草素等成分调控iNOS、p65等蛋白对气道炎症发挥治疗作用.This study aims to research the drug target and mechanism of Bashu granule on airway inflammation by network pharmacology,molecular docking simulation,cellular inflammation model.The composition and targets of the herbal of Bashu granule and the airway inflammation related targets were collected through the databases such as TCMSP and GeneCard.Enrichment analysis was used to analyze the biological physiological process and pathway of the related targets.PyMOL software was used to perform molecular docking between the screened potential active ingredients and the core protein target.The lipopolysaccharide(LPS)-induced macrophage inflammation model was established,and the effects of Bashu granule and different active ingredients on the expression of iNOS and p65 proteins were detected by Western-blot.The results of network pharmacology showed that there were 8 pharmacodynamic components and 9 action targets of Bashu granule for the treatment of airway inflammation.1368 physiological processes were obtained from GO enrichment analysis.134 related signaling pathways were obtained from KEGG enrichment.Protein molecular simulation docking showed that quercetin,kaempferol and luteolin had the lowest binding energy with AKT1 and MAPKs,which were the optimal binding sites.The results of cell experiments showed that the expression of iNOS protein in Bashu granule group was significantly lower than that in LPS group,and the phosphorylation of p65 protein was significantly inhibited.The predicted potential active ingredients could also reduce expression of iNOS to varying degrees.Bashu granules may exert therapeutic effects on airway inflammation through the regulation of iNOS,p65 and other proteins by components such as quercetin,kaempferol and luteolin.

关 键 词：巴蜀颗粒 气道炎症 网络药理学 分子对接 通路蛋白 

分 类 号：R285.5[医药卫生—中药学]