目的 探讨骨坏死康复丸治疗激素性股骨头坏死（Steroid-induced osteonecrosis of the femoral head， SONFH）的主要药理学基础和作用机制。方法 通过中药系统药理学数据库与分析平台（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP）等数据库对骨坏死康复丸的有效成分和 靶点进行筛选。基于人类在线孟德尔遗传数据库（Online Mendelian Inheritance in Man，OMIM）和 GeneCards 数 据库筛选 SONFH 的靶点。采用加权基因共表达网络分析（Weighted gene co-expression network analysis， WGCNA）对 SONFH 基因模块和枢纽基因进行鉴定。取三者的交集，获得骨坏死康复丸治疗 SONFH 的潜在靶 点，并利用 Cytoscape 软件构建的“活性成分-靶点”网络筛选关键活性成分；然后，利用 STRING 数据库构建 蛋白相互作用网络，筛选关键靶点。进行基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG） 信号通路富集分析，探索“关键活性成分-关键靶点-关键信号通路”之间的关系。最后，进行了关键活性成 分与关键靶点的分子对接，并使用 SONFH 大鼠模型进行实验验证。结果 得到骨坏死康复丸的 146 个化合物 和相应的 346 个靶点，获得了 4 187 个 SONFH 靶点。此外，基于 WGCNA 筛选出 SONFH 的 12 个基因模块和 2 556 个枢纽基因，得到槲皮素、木犀草素和山柰酚是骨坏死康复丸治疗 SONFH 的关键活性成分，涉及 PI3K/ AKT 等多条信号通路。分子对接显示关键活性成分与关键靶点之间存在较好的结合活性。动物实验结果证明 骨坏死康复丸可通过上调 AKT1、PI3K、RUNX2，下调 Caspase-3 和 IL-6 的表达改善骨生物学改变（P＜0.01）， 验证了网络药理学部分预测结果。结论 通过网络药理学和动物实验分析了骨坏死康复丸治疗 SONFH 的潜在 作用机制，可为进一步研究其药理基础和靶点提供参考。

Objective To investigate the main pharmacological basis and mechanism of action of Guhuaisi Kangfu Pill （GHSKF） in the treatment of steroid-induced osteonecrosis of the femoral head （SONFH） . Methods The active constituents and targets of GHSKF were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and other databases. The speculative targets of SONFH were screened out based on GeneCards and Online Mendelian Inheritance in Man （OMIM） databases. The gene modules and hub genes of SONFH were identified using a weighted gene co-expression network analysis （WGCNA） . The intersection of the two targets and the result of WGCNA was taken to obtain the potential targets of GHSKF for the treatment of SONFH. The key active constituents were screened with the “active constituent-target” network， which was constructed by the Cytoscape software. Then， the STRING database was used to construct the protein interaction network to screen the key targets. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis of key targets was performed， and the relationship between key active constituent， key targets and key signaling pathways was explored. Finally，the molecular docking between key active constituents and key targets was verified. In addition，the SONFH rat model was used for experimental verification. Results A total of 146 compounds and the corresponding 346 targets were identified based on the TCMSP database. A total of 4 187 targets of SONFH were obtained based on GeneCards and OMIM databases. In addition， twelve gene modules and 2 556 hub genes of SONFH were screened out based on WGCNA. Quercetin，luteolin and kaempferol were key active ingredients for the treatment of SONFH. Various signaling pathways such as PI3K/AKT were involved. Molecular docking showed the key active ingredients had good binding activity with the key targets. The results of animal experiments demonstrated that GHSKF could improve bone biological alterations by up-regulating AKT1， PI3K， RUNX2， and downregulating the expression of Caspase-3 and IL-6 （P＜0.01）， which verified some results of the network pharmacology prediction. Conclusion We analyzed the potential mechanism of action of GHSKF for the treatment of SONFH using network pharmacology and animal experiments，which may provide a reference for further research on its pharmacological basis and targets.

R285.5

河南省自然科学基金项目（242300420446）；河南省科技攻关项目（242102310496）