关键词: 绝经后骨质疏松症, 血管生成, 丙泊酚, Wnt/β-catenin信号通路

Abstract: Objective To investigate the impact of propofol on angiogenesis in postmenopausal osteoporosis (PMOP) rats and the role of Wnt/β-catenin signal pathway in this process. Methods Female Wistar rats were randomly grouped into sham operation group, PMOP group (bilateral ovariectomy), groups of propofol 2.5 mg/kg and of 5.0 mg/kg and propofol+Wnt inhibitor group (propofol 2.5 mg/kg + Wnt inhibitor 2 mg/kg), with 10 rats in each. The serum level of bone alkaline phosphatase (BALP), osteoprotegerin (OPG), nuclear factor κB receptor activating factor ligand (RANKL), vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) was detected by enzyme linked immunosorbent assay (ELISA); bone mineral density (BMD) of femur was measured by dual-energy X-ray absorptiometry; hematoxylin-eosin (HE) staining microscopy was applied to observe pathological changes of bone tissue; the expression of CD31 in bone tissue was detected by immunohistochemistry; Western blot was applied to detect the expression of bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), VEGFA, CD31, Wnt2, phosphorylated glycogen synthase kinase-3 (p-GSK-3) and β-catenin in bone tissue. Results Compared with the sham operation group, the serum RANKL level of PMOP group increased, the level of BALP, OPG, VEGF, Ang-1, expression of CD31 and protein level of BMP-2, Runx2, VEGFA, CD31, Wnt2, p-GSK-3, β-catenin all decreased (P＜0.05), the bone trabecula was damaged and the medullary cavity was enlarged; compared with the PMOP group, the changes of the above indexes in the propofol groups and the propofol+Wnt inhibitor group were obviously relieved(P＜0.05); compared with the propofol 5.0 mg/kg group, the propofol+Wnt inhibitor group showed inhibition in the activation of Wnt/β-catenin signal pathway, and weaken the promotion of propofol on angiogenesis, bone metabolism regulation and bone tissue morphology improvement in PMOP rats(P＜0.05). Conclusions Propofol may promote angiogenesis and regulate bone metabolism in PMOP rats by activating Wnt/β-catenin signal pathway as the potential mechanisms involved in anti-PMOP role process.

Key words: postmenopausal osteoporosis, angiogenesis, propofol, Wnt/β-catenin signal pathway