关键词: 右美托咪定, 骨质疏松, 骨微结构, Wnt/β-连环蛋白

Abstract: Objective To investigate the effects of dexmedetomidine (Dex) on osteoporosis (OP) rats and possible mechanisms. Methods The rats were divided into sham operation group, osteoporosis model group (OP, replicating the OP rat model with bilateral ovariectomies), Dex-L, M, and H (Dex low, medium, and high dose treatments) groups and Dex-H+XAV-939 group (Wnt/β-catenin pathway inhibitor). Micro-CT was applied to measure bone mineral density (BMD) and bone microstructure of rat femurs. The three-point bending experiment was applied to analyze the biomechanics of the femur (maximum load, fracture deflection, elastic modulus). HE staining was applied to observe pathological changes in the femur of rats. ELISA method was applied to evaluate bone metabolism indicators such as alkaline phosphatase(ALP), typeⅠ procollagen amino-terminal peptide (PINP) and typeⅠcollagen cross-linked C-telopeptide(CTX-Ⅰ). The expression of Runx2 and Wnt3a was examined by Immunohistochemistry. Western blot was applied to detect the protein expression of Runx2 and Wnt3a/β-catenin pathway in femoral tissue. Results Compared to the Sham group, the bone volume and number of trabeculae in OP group were obviously reduced, the maximum load, fracture deflection, elastic modulus, BMD, Tb.Th, Tb.N, BV/TV, ALP, PINP, Runx2, Wnt3a, β-catenin expression decreased, CTX-Ⅰ increased (P＜0.05). Compared to the OP group, the bone trabecular structure in the Dex-L, M, and H groups was restored, the maximum load, fracture deflection, elastic modulus, BMD, Tb.Th, Tb.N, BV/TV, ALP, PINP, Runx2, Wnt3a, β-catenin expression all increased but CTX-Ⅰ decreased (P＜0.05). Compared to the Dex-H group, the bone trabecular injury in the Dex-H+XAV-939 group showed a more severe damage. The maximum load, fracture deflection, elastic modulus, BMD, Tb.Th, Tb.N, BV/TV, ALP, PINP, Runx2, Wnt3a, β-catenin expression decreased while CTX-Ⅰ increased (P＜0.05). Conclusions Dex may antagonize OP effects by improving bone density, biomechanical properties and microstructure. The underlying mechanism might be related to the activation of the Wnt/β-catenin signaling pathway.

Key words: dexmetomidine, osteoporosis, bone microstructure, Wnt/β-catenin