栝楼桂枝汤治疗脑卒中后下肢痉挛的网络药理学研究

目的 基于网络药理学研究栝楼桂枝汤治疗脑卒中后下肢痉挛的作用机制。方法 利用TCMSP数据库、SwissTarget Prediction数据平台筛选栝楼桂枝汤活性成分靶点，并借助Gephi软件构建活性成分-靶点网络，运用Genecard、DisGeNET、TTD疾病数据库筛选作用于脑卒中、下肢痉挛靶基因，应用STRING平台构建靶蛋白相互作用网络，利用ClueGO软件对靶基因进行GO功能分析，通过DAVID v6.8平台对关键靶点KEGG通路进行分析。结果 栝楼桂枝汤中黄酮类、有机酸类、皂苷类等成分作用于IL6、TNF、EGFR、ESR1、TP53、STAT3、F2等49个关键靶基因；参与横纹肌细胞增殖、骨重塑、平滑肌细胞增殖正调控、肌细胞增殖、内皮细胞增殖等14类生物过程；调控TNF、MAPK、PI3K-Akt、ALS、神经营养、5-羟色胺能神经突触等30条信号通路。结论 栝楼桂枝汤多种活性成分通过抗炎、抗氧化、神经营养及保护等药理作用，以及参与肌细胞增殖等生物过程，从中枢神经系统及外周肌肉组织双向治疗脑卒中后下肢痉挛。

Study on network pharmacology of Gualou Guizhi Decoction in treatment of lower limb spasm after cerebral apoplexy

Objective The mechanism of Gualou Guizhi Decoction (GGD) in the treatment of lower limb spasm after stroke was analyzed based on network pharmacology. Methods Using the TCMSP and SwissTarget Prediction platform to screen the main components and targets of GGD, the obtained target information was imported into Gephi software to build the active components-targets network of GGD. Genecard, DisGeNET, and TTD disease databases were used to screen target genes for stroke and lower limb spasm; Target protein interaction network was constructed by using STRING platform; KEGG pathways, and GO (Gene Ontology) function were analyzed by using ClueGO software and DAVID v 6.8 platform. Results Flavonoids, organic acids, and saponins of GGD was applied to 49 key target genes, such as IL6, TNF, EGFR, ESR1, TP53, STAT3, and F2, etc; Forteen category biological processes including proliferation of striated muscle cells, bone remodeling, smooth muscle cells, muscle cells and endothelial cells proliferation were involved; Thirty signaling pathways, including TNF, MAPK, PI3K-Akt, ALS, serotonergic synapse, and neurotrophin, etc, were regulated. Conclusion Various active ingredients of GGD has pharmacological effects such as anti-inflammatory, antioxidant, neurotrophic, and participate in some biological processes, such as muscle cell proliferation, so as to treat lower limb spasm after stroke from central nervous system and peripheral muscle tissue two-ways.