| Objective To investigate the key targets and pathways for preventing bone loss caused by aromatase inhibitors (AIs) by tonifying the kidney and activating the blood. Methods Thirty mice were randomly divided into sham operation group, model group, and drug administration group. After castration, mice in the model group and drug administration group were subcutaneously injected with letrozole solution of 10 μg/d to establish an animal model of postmenopausal osteoporosis caused by AIs. Mice in the drug administration group was also given 19.24 g/(kg·d) of Huangqi Bushen Huoxue decoction (HQD) to prevent bone loss, while mice in the sham operation group and model group were given the same amount of normal saline. After three months of drug administration, the femurs of the mice were collected to test the bone mineral density and to verify the model. Results Compared to those in the blank group, the trabecular structure of the model group was loose and disordered, and the number was reduced, which proved that the model was successful. Compared to those in the model group, the trabecular bone in the drug group was thick and dense, and the number increased, which proved that the method of tonifying kidney and promoting blood circulation had a significant preventive effect. Compared to those in the blank group, 275 proteins were up-regulated and 189 proteins were down-regulated in the model group. Compared to those in the model group, 286 proteins were up-regulated and 898 proteins were down-regulated. There were 18 intersecting proteins among the three groups after comparison, including Ptbp1, Epx, Ear1, Ear2, Col6a5, Mta2, Alox15, Lztfl1, Ccl6, Diaph2, Wfdc21, Smarcb1, Strip1, C19orf12, Pex14, Akr1b7, Fahd1, and Nr1d2. Differential proteins were mainly involved in the regulation of cell development and differentiation, lipid metabolism, endonuclease activity, and other biological processes, and were significantly enriched in iron death, arachidonic acid metabolism pathway, troponin cytoskeleton regulation, and PI3K-AKT and other signal pathways. Conclusion Tonifying kidney and activating the blood effectively prevents bone loss caused by AIs. Its key target and mechanism may be related to Ptbp1, Alox15, iron death, and PI3K-AKT and other pathways. |