| Objective Animal experiments were conducted to explore the bone protection mechanism of rhizoma drynariae through ferroptosis pathway in ovariectomized osteoporotic rats. Methods Thirty SD rats were randomly divided into SHAM group, OVX group, and OVX-DR group. The rat model of ovaricectomy osteoporosis was constructed in the model group and the rhizoma drynariae group. Rats in the rhizoma drynariae group received bone crushing hydration decoction by intragastric administration. Rats in the remaining two groups received equal dose of normal saline. Micro-CT was used to detect the microstructures of the femoral bone. HE staining was used to observe changes in tissue morphology, Immunofluorescence was used to observe the expression of FTH1, SLC7A11, and GPX4. qRT-PCR was used to detect the mRNA expressions of FTH1, SLC7A11, GPX4, OPG, RUNX2, and RANKL in the blood and bone tissue of rats. Western blotting was used to detect the protein expressions of FTH1, SLC7A11, GPX4, OPG, RUNX2, and RANKL in rat bone tissue. Results ①Micro-CT showed that the bone mass in the model group was significantly lower than that in the sham operation group, and the bone mass in the rhizoma drynariae group was higher than that in the model group but lower than that inthe sham operation group.②HE staining results showed that the bone trabecular density in the model group was sparse, and the bone trabecular density in the rhizoma drynariae group was higher than that in the model group but lower than that in the sham operation group.③ Immunofluorescence results showed that the expressions of FTH1, SLC7A11, and GPX4 related to ferroptosis in the rhizoma drynariae group were higher than those in the model group but lower than those in the sham operation group, and the relative expressions of FTH1, SLC7A11, and GPX4 in the rhizoma drynariae group decreased (P<0.05). ④ mRNA expression levels of ferroptosis and osteoclasts in each group were detected using qRT-PCR. The results showed that compared with the model group, the mRNA expression levels of OPG, RUNX2, FTH1, SLC7A11 and GPX4 in the rhizoma drynariae group increased (P<0.05), while the mRNA expression of RANKL decreased (P < 0.05). Compared with the sham operation group, the mRNA expression levels of OPG, RUNX2, FTH1, SLC7A11, and GPX4 increased (P < 0.05), and the mRNA expression of RANKL decreased (P < 0.05). ⑤Results of WB detection of the protein levels of ferroptosis and osteoclast-related indicators in each group showed that compared with the model group, the protein levels of OPG, RUNX2, FTH1, SLC7A11, and GPX4 in the rhizoma drynariae group increased (P<0.05), while the protein level of RANKL decreased (P < 0.05). Compared with the sham operation group, the protein expression levels of OPG, RUNX2, FTH1, SLC7A11, and GPX4 increased (P<0.05), and the protein level of RANKL decreased (P<0.05). Conclusion Rhizoma drynariae reduces bone loss and prevents the occurrence of postmenopausal osteoporosis in ovariectomized rats, and its mechanism may be related to ferroptosis. |