Study on the mechanism of galangin promoting fracture in osteoporosis model rats / 中国药房

ABSTRACT

OBJECTIVE To preliminarily investigate the impacts of galangin （Gal） on fracture healing in osteoporosis （OP） model rats by regulating hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway. METHODS The OP rat model was constructed by using bilateral ovariectomy surgery. The model rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， Gal low-dose， medium-dose and high-dose groups （2.5， 5， 10 mg/kg）， inhibitor group （10 mg/kg Gal+100 mg/kg HIF-1α/VEGF signaling pathway inhibitor PX-478）， with 12 rats in each group. They were given relevant medicine intraperitoneally， once a day， for 90 consecutive days. The microstructure of rat bones was observed， the biomechanical status of rat femurs was evaluated， and the pathological damage and neovascularization of rat callus tissue were observed. The expression of platelet endothelial cell adhesion molecule-1 （PECAM-1） in the femur was detected. The contents of osteocalcin （OCN）， C-terminal telopeptides of type Ⅰ collagen （CTX-Ⅰ） and bone morphogenetic protein 2 （BMP-2） in serum were detected as well as the expressions of alkaline phosphatase （ALP） and HIF-1α/VEGF signaling pathway- related proteins in callus tissue. RESULTS Compared with the sham operation group， the BMD， BV/TV， Tb.N， Tb.Th， maximum load， the number and area of blood vessels， the average fluorescence intensity of PECAM-1， the contents of OCN and BMP-2， and the expression levels of ALP， HIF-1α and VEGF proteins in the model group were reduced significantly （P＜0.05）， while the content of CTX-Ⅰ increased significantly （P＜0.05）. Compared with the model group， the above indexes of rats were reversed significantly in Gal low-dose， medium-dose and high-dose groups （P＜0.05）， in a dose-dependent manner. Compared with the Gal high-dose group， the above indexes of rats were reversed significantly in the inhibitor group （P＜0.05）. CONCLUSIONS Gal can regulate bone metabolism， improve bone density of OP model rats and promote fracture healing， the mechanism of which may be associated with activating the HIF-1α/VEGF signaling pathway and promoting angiogenesis.