补肾健脾方调控HIF-1α/BNIP3介导的线粒体自噬影响细胞焦亡改善骨质疏松症的实验研究OA

Objective To investigate the molecular mechanism through which Bushen Jianpi Formula(补肾健脾方,BSJPF)amelio-rates bone status in osteoporotic rats,by regulating the HIF-1α/BNIP3 pathway-mediated mitochondrial mitophagy and influencing pyroptosis.Methods Sixty SD rats were randomly assigned to six groups:the blank,model,alendronate,and high/medium/low-dose BSJPF groups.Except for the blank group,an osteoporosis(OP)model was induced in all rats using dexamethasone.Drug interven-tions were administered concurrently for 5 consecutive weeks.Relevant indicators were measured after the intervention.Serum levels of ALP,PINP,IL-1β,and IL-18 were measured using ELISA.Micro-CT was performed for 3D reconstruction and bone mineral density(BMD)analysis of the distal femur.Histopathological changes in femoral tissues were observed via HE staining.The protein expression levels of mitophagy-related markers(HIF-1α,BNIP3,p62,and LC3)and pyroptosis-related markers(NLRP3,Caspase-1,and GSDMD)in femoral tissues were detected by Western blot(WB).Results BSJPF treatment significantly increased bone mineral density and ameliorated the histopathological structure of bone tissue.It upregulated the expression of HIF-1α and BNIP3,increased the LC3-II/LC3-I ratio,and modulated p62 expression.Concurrently,BSJPF downregulated the serum levels of IL-1β and IL-18,reduced reac-tive oxygen species(ROS)levels,and inhibited the expression of NLRP3,Caspase-1,and GSDMD proteins.Conclusion BSJPF allevi-ates bone deterioration in osteoporotic rats by regulating HIF-1α/BNIP3-mediated mitophagy and inhibiting pyroptosis.