世界中医药

目的：运用网络药理学方法探究枸杞子干预视网膜色素变性（RP）可能的作用机制。方法：检索国家知识基础设施数据库、中国学术期刊数据库、中文科技期刊数据库上正式公开发表的有关中药方剂治疗RP临床疗效的文献，记录其方剂中使用的中药名称及使用频数。运用中药系统药理学数据库与分析平台（TCMSP）筛选出枸杞子口服生物利用度≥30%和类药性≥0.18的化合物作为候选药效成分，根据TCMSP的“Related Targets”对枸杞子的活性成分的作用靶点进行预测，采用Cytoscape3.6.0软件构建化合物-靶点网络。通过DrugBank、DisGeNET数据库查找RP相关基因，通过STRING数据库进行蛋白质-蛋白质相互作用（PPI）分析。通过韦恩图将枸杞子活性成分靶点与RP疾病靶点取交集，得到枸杞子有效活性成分治疗RP的关键靶点。使用DAVID数据库对关键靶点进行GO功能注释和KEGG信号通路富集。结果：筛选出了62个中药方剂，共记录中药97种。其中使用频率最高的中药为枸杞子，共42次。得到枸杞子有对应靶点的活性成分29个，预测作用靶点188个，RP相关基因244个，枸杞子治疗RP的关键靶点12个，靶点参与的功能主要有基因表达的调控、细胞增殖、RNA转录调控、血管生成、缺氧等，主要的作用通路为PI3K-AKT信号通路、神经营养因子信号通路。结论：枸杞子可能通过PI3K-AKT信号通路、神经营养因子信号通路调节视神经细胞凋亡和视网膜神经退行性病变，保护视功能，从而达到治疗RP的目的。

English Summary:

To explore the possible mechanism of intervention of Lycii Fructus in Retinitis Pigmentosa(RP)by using network pharmacology.Methods:By searching the officially published literature on the clinical efficacy of traditional Chinese medicine(TCM)prescriptions in the treatment of RP，the names and frequency of Chinese medicine used in the prescriptions were recorded.Compounds with oral bioavailability of 30% or more and drug likeness of 0.18 or higher in Lycii Fructus were screened as candidate drug-effect ingredients by TCMSP database，and then the target of active ingredients of Lycii Fructus were predicted according to “Related Targets” of TCMSP.The ingredients-target interaction network was constructed by Cytoscape 3.6.0.The genes for RP was searched by DrugBank and DisGeNET，and the STRING database protein interaction analysis was performed.The target of active ingredients of Lycii Fructus intersected with the target of RP through the Venny diagram，through which the key targets of effective active ingredients of Lycii Fructus to treat RP are obtained.DAVID was used to perform GO function annotation and KEGG pathway enrichment on key targets.Results:A total of 62 TCM prescriptions and 97 Chinese medicines were recorded.The most frequently used Chinese medicine was Lycii Fructus，which was used for 42 times.A total of 29 active ingredients，188 predicted targets，and 244 genes related to RP were identified，as well as 12 key targets of effective active ingredients of Lycii Fructus to treat RP.The targets were involved in regulation of gene expression，cell proliferation，RNA transcription regulation，angiogenesis，hypoxia，etc.The main pathways were PI3K-AKT signaling pathway and neurotrophin signaling pathway.Conclusion:Lycii Fructus may regulate optic nerve cell apoptosis and retinal neurodegeneration through PI3K-AKT signaling pathway and neurotrophin signaling pathway to protect visual function and achieve the purpose of treating RP.

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