丹参治疗股骨头坏死的分子机制研究

Molecular Mechanism of Salvia miltiorrhizain Treatment of Femoral Head Necrosis

目的从分子机制角度入手,利用网络药理学方法探讨丹参治疗股骨头坏死的机制。方法筛选、预测丹参潜在的活性成分与靶点,工具为中药系统药理学数据库和分析平台。利用DrugBank、PharmGKB、HPO、GAD、OMIM、DisGeNET、TTD等数据库检索股骨头坏死相关作用靶点;结合生物信息学手段,明确丹参防治股骨头坏死的特异性靶点;采用ClueGo进行信号通路富集分析,以进一步分析其可能的分子机制。结果从中药系统药理学数据库和分析平台中检测出的与丹参相关的202个成分中,按照药物口服生物利用度和类药性参数得到65个入血活性成分,利用相关靶点预测技术预测可能的靶点103个;运用上述数据库检测,发现74个已知靶点与股骨头坏死相关。利用Cytoscape软件构建活性成分及疾病的蛋白质-蛋白质相互作用关系网络图,合并网络图并行拓扑分析筛选出关键基因130个;采用ClueGO信号通路富集分析显示,丹参作用于股骨头坏死的关键节点主要涉及75条信号通路,例如促进成骨细胞的骨形成与抑制破骨细胞的骨吸收信号通路。结论丹参治疗股骨头坏死具有多成分、多靶点的特点;其主要通路不仅是影响成骨细胞与破骨细胞的细胞生理过程,而且通过调节免疫和炎性反应等干扰和影响骨微环境,以控制疾病发展,与目前治疗股骨头坏死的作用机制相符合。

Objective To investigate the potential molecular mechanism of Salvia miltiorrhiza in the treatment of femoral head necrosis using the method of network pharmacology. Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to screen out and predict potential active components and targets of Salvia miltiorrhiza. DrugBank, PharmGKB, HPO, GAD, OMIM, DisGeNET, and TTD databases were used to search for the targets associated with femoral head necrosis. Specific targets involved in the prevention and treatment of femoral head necrosis by Salvia miltiorrhiza were identified with reference to bioinformatics methods. ClueGo was used for signaling pathway enrichment analysis to investigate the possible molecular mechanism. Results Among the 202 ingredients associated with Salvia miltiorrhiza detected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, 65 were identified as the active components entering the blood according to oral bioavailability and drug-likeness. A total of 103 potential targets were obtained by related target prediction techniques, and with the help of the above databases, 74 known targets were found to be associated with femoral head necrosis. The Cytoscape software was used to construct the protein-protein interaction network of active components and diseases, and 130 key genes were screened out by this network and topology analysis. The signaling pathway enrichment analysis using ClueGo showed that 75 signaling pathways were involved in the key nodes of the action of Salvia miltiorrhiza on femoral head necrosis, including the bone formation signaling pathway which promoted osteoblasts and the bone resorption signaling pathway which inhibited osteoclasts. Conclusion Salvia miltiorrhiza has the characteristics of multiple targets and components in the treatment of femoral head necrosis. Major pathways not only affect the physiological processes of osteoblasts and osteoclasts, but also affect and interfere with bone microenvironment through regulating immunity and inflammatory response to control disease progression, which is consistent with the current mechanism of the treatment of femoral head necrosis.