| 引用本文:王华星1，赵凯1，高雪1，李荣欣2，许筱颖1.基于网络药理学的玉屏风散和褪黑素对免疫系统影响的作用机制研究[J].世界中医药,2022,(11):. |
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| 基于网络药理学的玉屏风散和褪黑素对免疫系统影响的作用机制研究 |
| Effects of Melatonin and Yupingfeng Powder on Immune System in Mice Based on Network Pharmacology |
| 投稿时间：2021-11-30 |
| DOI：10.3969/j.issn.1673-7202.2022.11.009 |
| 中文关键词: 玉屏风散 褪黑素 免疫 网络药理学 靶点 通路 小鼠 作用机制 |
| English Keywords:Yupingfeng Powder Melatonin Immunity Network pharmacology Targets Pathways Mice Mechanism of action |
| 基金项目:国家自然科学基金面上项目（81573840） |
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| 中文摘要: |
| 目的：基于网络药理学探索玉屏风散和褪黑素对免疫系统的作用机制，比较二者异同，并以小鼠衰老模型对核心靶点进行验证。方法：利用中医药生物信息学数据库（SymMap）、毒理基因组学数据库（CTD）分别检索玉屏风散、褪黑素的作用靶点；利用生物信息分析软件（Cytoscape）的ClueGO插件进行基因本体（GO）免疫系统过程富集分析，提取二者的免疫过程相关靶点，并筛选其中的关键靶点；雄性8周龄无特定病原体（SPF）级昆明小鼠以D-半乳糖进行衰老造模，后分为常温对照、气温骤降、气温骤升3项，每项设对照组、玉屏风散组、褪黑素组、玉屏风散+褪黑素组，干预结束后摘眼球取血，使用酶联免疫吸附测定法检测血清白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）。结果：分别获取玉屏风散、褪黑素的作用靶点339个、325个；GO ISP分析显示作用靶点分别涉及11个、32个免疫过程，免疫相关靶点62个、84个，其中关键靶点20个、32个；关键靶点的京都基因和基因组百科全书（KEGG）通路富集分析显示关键靶点涉及33条、61条信号通路。动物实验结果表明，阳性结果均为在靶点的拓扑分析中排名位居前列者。结论：玉屏风散和褪黑素均可通过复杂的通路及靶点调控免疫系统，二者针对的通路较为一致，而靶点却相差较多，临床可考虑联合使用。 |
| English Summary: |
| To explore and compare the mechanism of Yupingfeng Powder and melatonin in regulating the immune system,and verify the core targets with the aging model of mice.Methods:The targets of Yupingfeng Powder and melatonin were searched in Symptom Mapping(SymMap) and Comparative Toxicogenomics Database(CTD),respectively.The ClueGO plug-in of Cytoscape was used for the gene ontology(GO) annotation of immune system process(ISP).The related targets were extracted,and the key targets were screened out.STRING was employed to build the protein-protein interaction(PPI) network of the key targets.The ClueGO plug-in was used for KEGG pathway enrichment analysis of the key targets.Eighty-four male SPF-grade mice aged 8 weeks were administrated with D-galactose at 1 000 mg/(kg·d) for 4 weeks.After that,they were assigned into three temperature groups:normal temperature group,temperature dropping group,and temperature rising group.Each temperature group was further assigned into a blank control group,a Yupingfeng Powder group,a melatonin group,and a Yupingfeng Powder+melatonin group.After the intervention,blood was collected from the eyeballs for the determination of serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α) by enzyme-linked immunosorbent assay(ELISA).Results:A total of 339 targets and 325 targets were obtained for Yupingfeng Powder and melatonin,respectively.GO annotation predicted 11 and 32 ISPs for Yupingfeng Powder and melatonin,which involved 62 and 84 targets,including 20 and 32 key targets,respectively.The P-values of PPI networks constructed with key targets were less than 3.33E-16 and 1.0E-16,respectively,with significant statistical significance.KEGG pathway enrichment showed that the key targets of Yupingfeng Powder and melatonin were mainly involved in 33 and 61 signaling pathways,respectively.In the experiments verifying the effects of Yupingfeng powder and melatonin on serum IL-1β,IL-6,and TNF-α levels in the elderly mice under different air temperatures,the positive results all ranked top in the topological analysis of targets.Conclusion:Both Yupingfeng Powder and melatonin can regulate the immune system through complex pathways and targets.They target similar pathways targeted but different targets.The combination of the two has certain advantages in clinical practice. |
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