掺锶聚磷酸钙修复股骨头坏死骨缺损过程中VEGF表达的实验研究

Expression of vascular endothelial growth factor in osteonecrosis of the femoral head during the repairing with biodegradable strontium-doped calcium polyphosphate

[目的]探讨应用新型材料掺锶聚磷酸钙(strontium-doped calcium polyphosphate,SCPP)修复兔激素性股骨头坏死骨缺损过程中血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)的表达及其意义。[方法]成年健康雄性日本大白兔21只,右侧臀肌注射甲泼尼龙20mg/kg,每日1次,共3次,建立兔激素性股骨头坏死动物模型。2周时随机处死3只动物取材组织学证实造模成功后,其余18只,通过髋关节后外侧入路活门法(Trap-door)清除骨坏死组织,制成双侧股骨头直径2.5mm×5mm的圆柱形骨缺损,随机分为3组。A组植入掺锶聚磷酸钙;B组植入聚磷酸钙:C组植入自体松质骨。术后4、8、12周分批处死各组动物,通过影像学、组织病理学、VEGF免疫组织化学染色观察评价股骨头坏死骨缺损修复过程中VEGF的表达及其意义。[结果]各组均未出现关节脱位,关节间隙正常。A组成骨细胞和成纤维细胞VEGF免疫反应性高,骨缺损区完全修复,大部分材料被新生骨小梁替代,缺损区骨密度接近于周围骨组织;B组VEGF免疫反应性较A组低,骨缺损区大部分修复,新生骨小梁替代部分材料,骨小梁较A组纤细稀疏,缺损区骨密度低于周围骨组织。C组骨缺损区修复,与周围骨组织融合,自体松质骨周围大量胶原纤维包裹并有新骨生成。[结论]应用具有促进血管生成作用的掺锶聚磷酸钙修复兔激素性股骨头坏死骨缺损过程中,可通过诱导VEGF表达促进新生血管生成加速骨修复过程。

[ Objective] To investgate the expression of vascular endothelial growth factor in osteonecrosis of the femoral head during the repairing with biodegradable strontium-doped calcium polypbospbate in glucocorticoid-induced rabbits. [ Method ] Twenty mg/kg methylprednisolone was injected into right gluteus medius muscle at intervals of 24 hours for three times in 21 adult male Japanese white rabbits. Three rabbits were killed randomly at 2 weeks after mcthylpednisolone injection, both the femora and humeri were histologically examined for the presence of osteonecrosis. The remaining 18 animals with a total of 36 cylindrical 2.5 × 5 mm femoral head defects were created following the trapdoor procedure. Eighteen animals with femoral head bone defects were randomly divided into three groups. Group A： the defects filled with strontium-doped calcium pelyphosphat, Group B： the defects filled with calcium polyphosphate and Group C： the defects filled with autologous cancellous bone alone. Roentgenographic and histological examinations were performed postoperatively. Finally, immunohistochemical analysis using monoclonal antibodies anti- VEGF was performed. [ Result] No hip joint dislocation occurred. In Group A, the results of VEGF expression had a significantly difference from those in the other groups 12 weeks after operation. Most of the biodegradable strontium-doped calcium polypbos- phate was resorbed and was largely replaced by newly formed trabocular bone at 12 weeks. While in Group B, a major part of defect were repaired. New formed trabecular bone in the defect was very thin. In Group C, morsellized cancellous bone was completely surrounded by fibrous and newly formed trabecular bone. [ Conclusion ] VEGF expression in the defect of osteonecrosis of the femoral head during the repairing with biodegradable strontium-doped calcium polypbosphate may play a role in stimulating vascular invasion and granulation tissue formation. This may be an important step toward facilitating the resorption in the osteonecrosis, thus impooring the repairing proceduce of femoral head defect.