激素性股骨头缺血坏死与Dickkopf-1及细胞凋亡的关系

摘要

背景;近年来已有许多学者开始探讨骨细胞和成骨细胞凋亡在激素性股骨头缺血坏死中的作用,对其发病机制有了新的认识.但遗憾的是,这些研究还尚未深入到对骨细胞、成骨细胞凋亡机制的研究中.有学者指出激素可以增加Wnt信号途径中的拮抗分子Dickkopf-1.目的:通过探索Dickkopf-1与细胞凋亡在激素性股骨头缺血坏死中的作用,了解Dickkopf-1及细胞凋亡与激素性股骨头缺血坏死的关系.方法:收集经全髋关节置换术取下的激素性股骨头缺血坏死股骨头标本14例作为实验组,新鲜股骨颈骨折髋关节置换术后标本8例作为对照组.电镜观察骨细胞形态变化,苏木精-伊红染色计数空缺骨陷窝,TUNEL法检测骨细胞凋亡,免疫组织化学法检测Dickkopf-1表达.采用Spearman线性相关分析法分析实验组的Dickkopf-1表达率与骨细胞凋亡指数的相关性.结果与结论:①实验组空缺骨陷窝率明显高于对照组,差异有显著性意义(P＜0.05);②实验组Dickkopf-1水平明显高于对照组,差异有显著性意义(P＜0.05);③实验组细胞凋亡指数明显高于对照组,差异有显著性意义(P＜0.05);④实验组中Dickkopf-1表达率与骨细胞凋亡指数呈正相关(r=0.623);⑤结果表明,Dickkopf-1与细胞凋亡共同参与了激素性股骨头缺血坏死的过程,Dickkopf-1水平升高可能是激素性股骨头缺血坏死发病的重要促进因素;骨细胞凋亡在股骨头缺血坏死过程中起重要作用.%BACKGROUND:The roles of osteocyte and osteoblast apoptosis in steroid-induced avascular necrosis of the femoral head (ANFH) have arouse much attention,and its pathogenesis has been understood gradually.But there is a lack of knowledge about the mechanisms underlying osteocyte and osteoblast apoptosis.Meanwhile,hormones have been shown to enhance the Dickkopf-1 expression in Wnt signaling pathway.OBJECTIVE:To investigate the roles of Dickkopf-1 and cell apoptosis in steroid-induced ANFH,and to understand their correlations with steroid-induced ANFH.METHODS:Necrotic femoral head samples were removed from 14 patients with steroid-induced ANFH after total hip arthroplasty (experimental group),and normal femoral heads were from 8 patients with femoral neck fracture (control group).The cellular morphology was observed using transmission electron microscope;the number of empty lacunae was counted through hematoxylin-eosin staining;the cell apoptosis was detected by TUNEL assay;the expression level of Dickkopf-1 was detected by immunohistochemistry.Moreover,the correlation between the Dickkopf-1 positive rate and apoptosis index of osteocytes was analyzed by Spearman rank correlation analysis.RESULTS AND CONCLUSION:The number of empty lacunae,expression level of Dickkopf-1,and apoptosis index of osteocytes in the experimental group were significantly higher than those in the control group (P ＜ 0.05).In the experimental group,the Dickkopf-1 positive rate was positively correlated to the apoptosis index of osteocytes (r=0.623).These results indicate that Dickkopf-1 and osteocyte apoptosis both play key roles in steroid-induced ANFH,and increased Dickkopf-1 level may promote the development of ANFH.