Abstract:Objective : Through the comprehensive strategy of LC / MS analysis technology and network pharmacology, combined with experimental verification, the effective components and mechanism of Bushen Zhuanggu Decoction in the treatment of diabetic osteoporosis were discussed. Methods : UPLC-Q-Orbitrap-MS method was used to analyze and identify the effective chemical components in Bushen Zhuanggu Decoction. The genes related to DOP and ferroptosis in the database were retrieved, and the intersection was obtained to obtain the potential targets of active ingredients for the treatment of DOP by regulating ferroptosis pathway. DOP rat model was induced by intraperitoneal injection of streptozotocin combined with high-sugar and high-fat feeding. After the model was successfully constructed, Bushen Zhuanggu Decoction was administered for 8 weeks. Body weight, blood glucose and glycosylated hemoglobin were measured. Micro-CT was performed to obtain bone morphological changes. Iron ion levels, SOD and MDA levels were detected by kits. Western blot was used to detect the expression of Nrf2 / HO-1 signal and ferroptosis-related protein in bone tissue. Results : 1.A total of 848 targets of 46 identified compounds were predicted in the blood compounds of Bushen Zhuanggu Decoction. By comparing GeneCards, CTD database and FerrDb database, 81 potential targets of Bushen Zhuanggu Decoction against DOP by regulating ferroptosis were finally obtained. PPI network analysis of SIRT1, MTOR, STAT3, NFE2L2, SRC, EGFR, IL6, MAPK3, IL1B, PPARG, ALB and other nodes may be important targets for Bushen Zhuanggu Decoction in the treatment of DOP. Through KEGG pathway enrichment analysis, 134 signaling pathways about intersection target genes were obtained. The main pathways were metabolic pathways, lipid and atherosclerosis, ferroptosis signaling pathways in diabetic complications, etc. The results of in vivo experiments showed that compared with the normal group, the body weight of rats in the model group increased slowly, the levels of blood glucose and glycosylated hemoglobin increased, the trabecular bone was destroyed, the bone mineral density, bone volume fraction, trabecular thickness and density decreased, the degree of trabecular separation increased, the levels of iron ions and MDA in bone tissue increased, the activity of SOD decreased, and the expression of Nrf2, HO-1 and ferroptosis-related proteins increased ; Compared with the model group, the weight gain of rats increased, the levels of blood glucose and glycosylated hemoglobin decreased, the destruction of bone trabecula decreased, the bone mineral density, bone volume fraction, bone trabecula thickness and density increased, the separation of bone trabecula decreased, the levels of iron ions and MDA in bone tissue decreased, the activity of SOD increased, and the expression of Nrf2, HO-1 and ferroptosis-related proteins decreased. Conclusion : Bushen Zhuanggu Decoction has the characteristics of multi-component, multi-target and multi-pathway in the treatment of T2DOP. The results of in vivo experiments show that Bushen Zhuanggu Decoction can prevent and treat DOP by regulating Nrf2 / HO-1 signaling pathway and inhibiting oxidative stress and ferroptosis.