基于网络药理学和分子对接技术的丹贝益肺方对肺纤维化干预作用研究  

Study on the effect of Danbei Yifei formula on pulmonary fibrosis based on network pharmacology and molecular docking technology

作　　者：蔡萧君 江柏华 陆振华 王涛 张碧海 王旭玲 CAI Xiao-jun;JIANG Bai-hua;LU Zhen-hua;WANG Tao;ZHANG Bi-hai;WANG Xu-ling(Heilongjiang Academy of Traditional Chinese Medicine,Harbin 150036,China)

机构地区：[1]黑龙江省中医药科学院,黑龙江哈尔滨150036

出　　处：《海南医学院学报》2022年第5期363-368,376,共7页Journal of Hainan Medical University

基　　金：黑龙江省应用技术研究与开发计划课题(GA19C1080)。

摘　　要：目的:确定丹贝益肺方对肺纤维化干预作用的药效物质基础及作用机制。方法:以丹贝益肺方明确的入血成分或符合里宾斯基五规则的潜在药效成分入手,采用中药网络药理学方法和技术对丹贝益肺方所含中药,如丹参、平贝、桃仁等的体内作用靶标进行预测和分析。在此基础上通过富集分析明确丹贝益肺方治疗肺纤维化的核心通路,并通过分子对接技术进行模拟和验证,确定药物配体和蛋白靶标相作用的结合能,评价其亲和力和稳定性。阐明丹贝益肺方治疗肺纤维化的药效物质基础和作用机制。结果:中药网络药理学预测结果显示丹贝益肺方包含72个潜在药效成分和相应的26个靶点,包括CHRM1、MAPK14、CCL2、ADRB1、PTGS1、PPARG、ALOX5、Pde3a、CHRM2、Adrb2、TNF、JUN、Adora2a、LTA4H、CYP1A2、OPRD1、CHRM3、DRD2、OPRM1、ARG1、EDNRA、Il6st、TACR1、MMP1、MMP8、Ptgs2,这些靶标与肺纤维化及肺部相关疾病高度相关。GO功能富集分析得到GO条目26个(P<0.05),其中生物过程22个,细胞组成9个,分子功能3个。网络药理学结果显示多个成分如原儿茶酸、氨基琥珀酸等都与肺纤维化已知靶标有直接作用关系。结论:丹贝益肺方包含多个与肺纤维化有抑制作用的药效成分,其可能通过多成分多靶标协同起效的作用机制发挥药效。Objective:To determine the pharmacodynamic material basis and mechanism of Danbei Yifei formula on pulmonary fibrosis.Methods:Based on the clear absorbed components of Danbei Yifei formula or the potential effective components in line with the five rules of Ribinsky,the network pharmacology method and technology of traditional Chinese medicine were used to predict and analyze the action targets of Danbei Yifei formula in vivo,such as Salvia miltiorrhiza,Pingbei,Taoren,etc.On the basis of enrichment analysis,the core pathway of Danbei Yifei formula in the treatment of pulmonary fibrosis was identified,and the binding energy of drug ligand and protein target was determined through molecular docking technology simulation and verification,and its affinity and stability were evaluated to clarify the material basis and mechanism of Danbei Yifei formula in the treatment of pulmonary fibrosis.Results:The results of network pharmacology prediction of traditional Chinese medicine showed that Danbei Yifei formula contained 72 potential pharmacodynamic components and 26 corresponding targets,including CHRM1,MAPK14,CCL2,ADRB1,PTGS1,PPARG,ALOX5,Pde3 a,CHRM2,Adrb2,TNF,JUN,Adora2 a,LTA4 H,CYP1 A2,OPRD1,CHRM3,DRD2,OPRM1,ARG1,EDNRA,Il6 st,TACR1,MMP1,MMP8,and Ptgs2,which were highly related with pulmonary fibrosis and pulmonary fibrosis lung related diseases.There were 26 GO items(P<0.05)in GO functional enrichment analysis,including 22 biological process,9 cellular component and 3 molecular function categories.The results of network pharmacology showed that many components,such as protocatechuic acid and aminosuccinic acid,had direct effects on known targets of pulmonary fibrosis.Conclusion:Danbei Yifei formula contains many effective components which have inhibitory effects on pulmonary fibrosis,and it may play its role through the mechanism of multi-component and multi-target synergistic effect.

关 键 词：丹贝益肺方 肺纤维化 网络药理学 原儿茶酸 花生四烯酸5-脂加氧酶 

分 类 号：R285[医药卫生—中药学]