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目的：基于网络药理学并通过动物实验和分子对接技术验证，初步探讨六味补气方干预COPD的作用及其机制。方法：采用在线数据库筛选六味补气方的主要活性成分及其对应靶点蛋白和COPD基因，并选取交集基因；通过STRING数据库构建蛋白互作（PPI）网络分析；利用David数据库对交叉靶点进行基因本体（GO）、京都基因与基因组百科全书（KEGG）富集分析。采用Autodock Tools和Py MOL进行分子对接并进行可视化处理。使用脂多糖（LPS）联合烟熏法建立SD雄性大鼠COPD模型，给予六味补气方进行干预后进行样本采集。通过检测大鼠肺功能指标，HE染色观察肺组织病理变化及ELISA法检测肺组织匀浆中白介素10(IL-10)水平对网络药理学预测结果进行验证。结果：网络药理学分析得到复方有效成分76个，潜在靶点768个。GO富集分析得到884个GO条目；KEGG富集分析得到139条信号通路。分子对接显示：六味补气方治疗COPD的主要活性成分为山奈酚、槲皮素、油酸、β-谷甾醇和川陈皮素等。六味补气方与COPD的核心靶点肿瘤坏死因子（TNF）、RAC-α丝氨酸/苏氨酸蛋白激酶（AKT1）、白介素6(IL-6)和IL-10有较好的结合能。实验研究发现，与正常组比较，模型组大鼠肺功能降低（P<0.01），肺组织中出现慢性支气管炎和肺气肿病理变化，肺组织匀浆中IL-10水平下降（P<0.01）。与模型组比较，各用药组肺功能改善（P<0.01），支气管肺组织炎症反应和病理变化改善，肺组织匀浆中IL-10水平上升（P<0.01）。结论：六味补气方通过多成分，多靶点及多信号通路的作用，增强肺功能，减轻支气管与肺组织的病理特征并抑制炎症反应，其中抑炎因子IL-10可能发挥主要作用。
Abstract：Objective: To investigate the mechanism of the compound Chinese medicine of Liuwei Buqi decoction in the treatment of chronic obstructive pulmonary disease(COPD) based on network pharmacology,molecular docking and animal experiments. Methods: Using the online databases to obtain the relevant chemical ingredients,target proteins of Liuwei Buqi decoction and related disease genes, to choose the intersection genes,and to build protein interaction(PPI) network analysis by STRING databases, relating targets for gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis by David databases.Using the Autodock Tools and Py MOL to achive the molecular docking and visual process.Establishing the COPD model by lipopolysaccharide(LPS) combined with cigarette smoking.Givig Liuwei Buqi decoction to intervent and collecting samples after drug intervention.The prediction results of network pharmacology were verified by detecting the lung function,and the pathological changes of lung tissue by H&E staining and detecting the level of interleukin-10(IL-10) in lung tissue homogenate were by ELISA. Results: Network pharmacology analysis identified 76 active components and 768 potential targets.GO enrichment analysis obtained 884 GO entries. KEGG enrichment analysis obtained 139 signaling pathways.The molecular docking results showed that the main active ingredients of Liuwei Buqi decoction in the treatment of COPD are kaempferol,quercetin,oleic acid,β-sitosterol and nobiletin.Liuwei Buqi decoction has a good binding energy with TNF,AKT1,IL-6and IL-10,which are the core targets of COPD.Experimental results discoverd that compared with the normal control group, the lung function of the model group was decreased(P<0.01). Chronic bronchitis and pulmonary emphysema occured in the lung tissue.The level of IL-10 was decreased(P<0.01). Compared with the model group, the lung function of each medication group was improved(P<0.01, P<0.05). The pathological changes of bronchopulmonary tissues were improved. The level of IL-10 in lung tissue was increased(P<0.01). Conclusion: Liuwei Buqi decoction can increase lung function,relieve the pathological changes of COPD bronchial and lung tissue and inhibit the inflammatory response by multiple components, targets and signaling pathways.The suppression of inflammation factor IL-10 may play an significant role.
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基本信息:
DOI：10.13210/j.cnki.jhmu.20241126.002
中图分类号:R285.5
引用信息:
[1]赵晶燕,吴柏合,栾雪婧,等.基于网络药理学和动物实验探讨六味补气方对慢性阻塞性肺疾病的干预作用[J].海南医科大学学报,2025,31(13):1007-1021.DOI:10.13210/j.cnki.jhmu.20241126.002.
基金信息:
安徽省自然科学基金资助项目（1708085MH222）~~
2024-11-26
2024-11-26
2024-11-26