Protective effects of salidroside on ovariectomized osteoporosis rats based on the HIF-1α/VEGF signaling pathway
TIAN Chenchen
ZHANG Peng
QI Lin
Abstract：Objective To investigate the role of salidroside(SAL)in protecting osteoporosis in ovariectomized rats by regulating the hypoxia-inducible factor 1alpha(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods An osteoporosis rat model was created by surgical removal of bilateral ovaries.Totally 36 ovariectomized rats were randomly divided into four groups:ovariectomized model group(OVX group),low-dose SAL group(SAL-L group,4.0mg·kg-1·d-1),high-dose SAL group(SAL-H group,20.0mg·kg-1·d-1)and positive drug raloxifene(RLX)group(4.0mg·kg-1·d-1),with 9 rats per group.Sham operation group(SHAM group)was set up as a control,including 9 rats.After 3 months of gavage administration,the rats were sacrificed.Rat femur was taken to measure the bone mineral density(BMD),the ratio of femoral wet/dry/ash weight to volume,and femoral biomechanical parameters.Serum levels of calcium,phosphorus,alkaline phosphatase(ALP),bone gal protein(BGP)and 17beta-estradiol(E2)were measured.Immunohistochemistry was used to detect bone tissue hypoxia,expression levels of HIF-1α and VEGF and vascular density.Results Compared with the SHAM group,rats in the OVX group had significantly lower femoral BMD,femoral wet/dry/ash weight-to-volume ratio,E2 level and femoral biomechanical parameters,but higher serum calcium,phosphorus,ALP and BGP(P＜0.05),which could be significantly reversed by high-dose SAL and RLX.It was suggested that SAL effectively protected against osteoporosis.Immunohistochemistry results showed that compared with the SHAM group,the expression of hypoxyprobe-1 in rat bone tissue of the OVX group was significantly higher(P＜0.05),suggesting the condition of hypoxia in the bone tissue of rats after ovariectomy.The expression of hypoxyprobe-1 in the SAL-H and RLX groups was significantly lower than that of the OVX group(P＜0.05),proving that both high-dose SAL and RLX significantly alleviated hypoxia in bone tissue.In addition,compared with the SHAM group,the expressions of HIF-1α,VEGF,and cluster of differentiation 31(CD31)in the bone tissue of the OVX group increased significantly(P＜0.05).Compared with the OVX group,the expressions of HIF-1α,VEGF,and CD31 in the bone tissue of the RLX group and SAL-H group increased significantly(P＜0.05),indicating that SAL promoted the formation of bone blood vessels and alleviated osteoporosis in ovariectomized rats by regulating the HIF-1α/VEGF signaling pathway.Conclusion SAL attenuates osteoporosis in ovariectomized rats via regulating the HIF-1α/VEGF signaling pathway.
Keywords：osteoporosissalidrosidehypoxia-inducible factor 1alpha(HIF-1α)vascular endothelial growth factor(VEGF)
Publication Date：2025-10-26
Online Publishing Date：2025-11-19(First online date of this platform, not the publication date of the document)
Pages：6( 1605-1610 )