目的：探究鹿仲健骨汤治疗股骨头坏死(Osteonecrosis of the Femoral Head, ONFH)的作用机制。方法：采用动物实验验证鹿仲健骨汤对股骨头坏死的治疗作用，运用网络药理学筛选作用靶点，分子对接验证配体与受体之间的关联度。采用维甲酸灌胃的方式建立股骨头坏死大鼠模型，50只大鼠随机分为空白组、模型组及鹿仲健骨汤高、中、低剂量组。通过股骨头部位骨形态计量学、骨组织病理学、成骨相关蛋白表达情况评价鹿仲健骨汤对股骨头坏死的治疗作用，运用UHPLC-QE-MS非靶向代谢组学技术检测血清代谢差异物，进行代谢通路富集分析，整合网络药理学与代谢组学，并采用分子对接深入研究作用机制。结果：实验验证结果显示，与对照组相比，鹿仲健骨汤可以显著提高OCN、OPN等成骨因子的表达(P＜0.01)，骨密度增加，骨小梁有不同程度的改善。代谢组学检测结果显示，与模型组相比，鹿仲健骨汤可回调34种血清代谢差异物，涉及到21条代谢通路，主要代谢通路为花生四烯酸代谢、类固醇激素生物合成、初级胆汁酸生物合成、赖氨酸降解等。通过网络药理学分析，共获得鹿仲健骨汤185个成分，得到1040个成分靶点、551个疾病靶点和76个交集靶点，KEGG分析显示主要涉及HIF-1、甲状腺激素信号转导途径、钙离子等信号通路；整合分析显示鹿仲健骨汤可能通过精氨酸和脯氨酸代谢、花生四烯酸代谢、类固醇激素生物合成等7条代谢途径治疗ONFH；结论：鹿仲健骨汤通过影响花生四烯酸代谢、类固醇激素生物合成等代谢通路，调节骨代谢，增加骨密度，起到治疗ONFH的作用。

OBJECTIVE: To explore the mechanism of Luzhongjiangu Decoction in treating Osteonecrosis of the Femoral Head (ONFH). METHODS: Experimental verification, network pharmacology, molecular docking and metabolomics were used to investigate the effect of Luzhongjiangu Decoction on ONFH. Animal experiments were carried out to verify the effect of Luzhongjiangu Decoction on the rat model with ONFH, which was established by intragastric administration of retinoic acid. Fifty rats were randomly divided into blank group, model group, high-, medium- and low- dose Luzhongjiangu Decoction groups. After treatment, the therapeutic effect was evaluated by bone histomorphometry, bone histopathology and the expression of osteogenic related proteins. The serum metabolic differences were detected by UHPLC-QE-MS non-targeted metabonomics technique. Network pharmacology, molecular dockingwere used to investigate the effect of Luzhongjiangu Decoction on ONFH. RESULTS: The experimental results showed that Luzhongjiangu decoction can significantly increase the expression of OCN, OPN and other osteogenic related factors, alleviate the destruction of bone trabeculae, increase bone mineral density, compared with that in the model group (P＜0.01). The metabolomics test showed that compared with model group, Luzhongjiangu decoction could callback 34 kinds of serum metabolic differences, involving 21 metabolic pathways, the main metabolic pathways were arachidonic acid metabolism, steroid hormone biosynthesis, primary bile acid biosynthesis, lysine degradation and so on. Network pharmacological results suggested that 185 active components and 1040 targets 551 disease targets and 76 intersection targets were obtained. The key pathways of Luzhongjiangu Decoction in the treatment of ONFH, which were analyzed by KEGG, involved HIF-1 signaling pathway, thyroid hormone signaling pathway, Calcium signaling pathway and so on. Integrated analysis showed that Luzhongjiangu Decoction may treat ONFH through seven metabolic pathways including arginine and proline metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis; the molecular docking results also revealed correlation between potential pharmacodynamic substances and core target genes. CONCLUSION: Luzhongjiangu decoction can regulate bone metabolism and increase bone mineral density by affecting the metabolic pathways such as arachidonic acid metabolism and steroid biosynthesis.

济南市“新高校20条”(202228121)；山东省技术创新引导计划(中央引导地方科技发展基金)(YDZX2024122)；山东省民办教育协会科研课题(MJ202466)