激素性股骨头坏死过程中低氧诱导因子1α与骨细胞凋亡

背景：激素性股骨头缺血坏死发病机制未明，缺血缺氧是其根本原因，缺氧状态下低氧诱导因子1α参与多种信号通路传导。作者的前期研究发现，骨细胞凋亡与激素性股骨头缺血坏死存在关联。 目的：分析低氧诱导因子1α和骨细胞凋亡是否与激素性股骨头缺血坏死存在关联。 方法：选健康5月龄新西兰白兔20只，随机分为空白对照组和实验组，每组10只。实验组兔给予激素联合内毒素制备激素性股骨头缺血坏死模型。最后一次给药后第4周处死所有实验动物，取双侧后肢股骨头，光镜与电子显微镜下观察形态与超微结构变化，计算各组空缺骨陷窝；应用免疫组织化学技术检测低氧诱导因子1α表达，应用TUNEL法检测骨细胞凋亡。 结果与结论：实验组空缺骨陷窝率高于空白对照组(P < 0.01)；实验组骨细胞凋亡高于空白对照组(P < 0.01)；实验组低氧诱导因子1α低于空白对照组(P < 0.01)；实验组中低氧诱导因子1α表达与细胞凋亡率呈负相关(r=-0.675)，实验组中空缺骨陷窝率与细胞凋亡率呈正相关(r=0.793)。结果说明，在激素性股骨头缺血坏死早期，低氧诱导因子1α的低表达与骨细胞凋亡存在相关性，二者参与了激素性股骨头缺血坏死的病理变化过程，骨细胞的死亡方式为凋亡。 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Hypoxia inducible factor-1 alpha and apoptosis of osteocytes in steroid-induced avascular necrosis of the femoral head

BACKGROUND: Although the pathogenesis of steroid-induced avascular necrosis of the femoral head is unknown, ischemia/hypoxia is the fundamental reason. Under hypoxic conditions, hypoxia-inducible factor-1α is involved in various signal transduction pathways. Preliminary studies have found that osteocyte apoptosis is associated with steroid-induced avascular necrosis of the femoral head. OBJECTIVE: To investigate the relationship between hypoxia inducible factor-1α and apoptosis in steroid-induced avascular necrosis of the femoral head. METHODS: Twenty New Zealand white rabbits, 5 months old, were randomly divided into control group and experimental group, 10 rabbits in each group. Animal models of avascular necrosis of the femoral head were  made in the experimental group using steroid and endotoxin. Four weeks after the final administration, all animals were sacrificed to take the bilateral femoral heads that were observed morphologically and ultrastructurally under electron microscope. Number of vacant lacunae was calculated in each group. Immunohistochemical technique and TUNEL methods were used to detect hypoxia inducible factor-1α and osteocyte apoptosis, respectively. RESULTS AND CONCLUSION: Lacuna vacancy rate of the experimental group was higher than that of the control group (P < 0.01); the osteocyte apoptosis rate of the experimental group was higher than that of the control group     (P < 0.01). In the experimental group, the apoptosis rate was negatively correlated with the expression of hypoxia inducible factor-1α (r=-0.675), but positively correlated with the lacuna vacancy rate (r=0.793). These findings indicate that in the early stage of steroid-induced avascular necrosis, low expression of hypoxia-inducible factor-1α is related with apoptosis of osteocytes, and they are both involved in the pathological process of femoral head necrosis. Apoptosis is the death way of osteocytes.