目的 研究六味地黄丸治疗小儿脑瘫的疗效并使用网络药理学探讨作用机制。方法 选取2021年6月至2021年10月临沂市中医院收治的46例肝肾亏损型PCP患儿作为研究对象，按随机数字表法分成对照组与药物组各23例，对照组给予常规儿童康复治疗，药物组在常规康复治疗基础上给予六味地黄丸治疗，连续治疗4周后观察患儿粗大运动功能测试量表（GMFM）评分的改善情况。使用网络药理学方法获取六味地黄丸的活性成分、靶点与PCP疾病靶点，得到交集靶点后构建交集靶点蛋白质相互作用网络并进行富集分析。结果 药物组疗效评分显著高于对照组（P=0.033），筛选得到6味中药47个主要成分与99个疾病治疗靶点，发现10个关键靶点为：TP53、AKT1、JUN、TNF、MAPK1、IL6、HSP90AA1、RELA、MAPK8、VEGFA，通过靶点富集获取GO条目558个，KEGG条目99个，主要富集到PI3K-Akt信号通路、TNF信号通路、HIF-1信号通路、MAPK信号通路、Toll样受体信号通路等发挥治疗作用。结论 六味地黄丸可通过多成分、多靶点、多通路发挥显著疗效，临床治疗PCP优于常规康复治疗。本文以临床为基础，借助网络药理学探讨六味地黄丸治疗PCP疗效显著的作用机制，分析研究流程符合《网络药理学评价方法指南》要求，具有可靠性、规范性与合理性，为临床应用中药防治PCP提供了案例与理论依据。

Objective To study the curative effect of Liuwei Dihuang Pills in the treatment of pediatric cerebral palsy (PCP) and to explore the mechanism of clinical efficacy by using network pharmacology.Methods 46 PCP children with liver and kidney deficient who treated in Linyi Traditional Chinese Medicine Hospital from June 2021 to October 2021 were randomly divided into control group and drug group, with 23 cases in each group. The control group was given routine rehabilitation treatment, the drug group was given Liuwei Dihuang Pills on the basis of routine rehabilitation treatment. After 4 weeks of continuous treatment, the improvement of the Gross Motor Function Measure (GMFM) score was observed. Network pharmacology was used to retrieved the active ingredients and targets of Liuwei Dihuang Pills and the disease targets of PCP. After obtained the intersection targets, the protein-protein intersection (PPI) network was constructed, and bioaccumulation was analyzed.Results The efficacy score of the drug group was significantly higher than that of the control group (P=0.033). The screening analysis revealed 47 main components and 99 therapeutic targets of 6 Chinese medicines. And 10 key targets were found: TP53, AKT1, JUN, TNF, MAPK1, IL6, HSP90AA1, RELA, MAPK8, VEGFA. 588 GO items and 99 KEGG items were obtained through target enrichment, which were mainly related to PI3K-Akt signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway, etc. to play a therapeutic role.Conclusion Liuwei Dihuang Pills can exert significant effects through multi-component, multi-target and multi-pathway. The clinical treatment of PCP is better than conventional rehabilitation. Based on clinical practice, this paper discusses the effective mechanism of Liuwei Dihuang Pill in the treatment of PCP with the help of network pharmacology. The analysis and research process meets the requirements of Network pharmacology evaluation method guidance-Draft, which is reliable, standardized and reasonable. It provides a case and theoretical basis for the clinical application of traditional Chinese medicine in the prevention and treatment of PCP.

R285.5

山东省卫生健康委员会面上项目（2018WS201）：基于PI3K/Akt通路研究脑缺血神经干细胞定向迁移的作用机制，负责人：于少泓。