骨髓造血细胞DNA氧化损伤与骨细胞凋亡在早期激素性股骨头坏死中的表现

摘要

BACKGROUND:Hormones-induced avascular necrosis of the femoral head is a complex biological process, and its pathogenesis remains unclear. To prove its etiologic mechanism is stil the focus of research in this field. OBJECTIVE:To discuss the pathological changes of hematopoietic cels and osteocytes in early avascular necrosis of the femoral head induced by glucocorticoids . METHODS: Forty Japanese white rabbits, 4 months old, were randomly divided into glucocorticoids+ lipopolysaccharide group (combination group), glucocorticoids group, lipopolysaccharide group and blank control group, with 10 rabbits in each group. Five animals from each group were sacrificed at 2 and 4 weeks after the last dosing, respectively. Vacant bone lacunae were counted under optical microscope, morphology of osteocytes was observed under electron microscope, osteocyte apoptosis was assay by TUNEL, and DNA oxidative damage to hematopoietic cels was detected by immunohistochemistry. n RESULTS AND CONCLUSION:Compared with the other three groups, the rates of vacant lacunae and DNA oxidative damage to hematopoietic cels in the combination group were significantly higher at 2 and 4 weeks after treatment as wel as the apoptosis rate of osteocytes at 4 weeks after treatment (P < 0.01); while there were no statistical differences between the other three groups. In the combination group, the vacant rate of bone lacunae and apoptosis rate of osteocytes were positively correlated (r=0.793). These findings indicate that DNA oxidative damage to hematopoietic cels and apoptosis of osteocytes participate in the pathological changes of early avascular necrosis of the femoral head induced by glucocorticoids. The former is prior to the latter, and the death manner of osteocytes is apoptosis.%背景：激素导致股骨头缺血坏死是一个复杂的生物学过程，其发病机制仍不清楚，探明其病因学机制，仍然是该领域研究的重点。目的：观察骨髓造血细胞DNA氧化损伤与骨细胞凋亡在早期激素性股骨头缺血坏死中的病理改变。方法：4月龄日本大耳白兔40只，随机数字表法分为4组，每组10只。其中3组兔分别给予激素联合内毒素、单纯激素、单纯内毒素处理，另1组做空白对照。分别于最后一次给药后第2，4周处死实验动物，每次每组5只。光镜下计数各组兔股骨头空缺骨陷窝、电镜观察骨细胞形态变化、TUNEL法检测骨细胞凋亡、免疫组织化学法检测骨髓造血细胞DNA氧化损伤。结果与结论：与其他3组比较，激素联合内毒素组第2，4周空缺骨陷窝率、骨髓造血细胞DNA氧化损伤率及第4周骨细胞凋亡率均显著增高(P <0.01)；其他3组之间空缺骨陷窝率、骨髓造血细胞DNA氧化损伤率及骨细胞凋亡率各指标比较差异无显著性意义。激素联合内毒素组空缺骨陷窝率与细胞凋亡率呈正相关(r=0.793)。结果提示在激素性股骨头缺血坏死早期，骨髓造血细胞DNA氧化损伤与骨细胞凋亡参与了激素性股骨头缺血坏死的病理变化过程，前者先于后者发生，骨细胞的死亡方式为凋亡。