激素对股骨头微血管及组织细胞的影响

目的通过建立激素性股骨头缺血性坏死动物模型,研究股骨头微血管密度(microvas-culardensity,MVD)和股骨头组织细胞超微结构的变化,探讨长期大剂量使用糖皮质激素引起股骨头缺血性坏死的机制。方法健康日本白兔40只,1.86～2.21kg,平均2.06kg。随机分为两组,实验组31只,对照组9只。实验组每周皮下注射醋酸氢化泼尼松8mg/kg,对照组每周皮下注射生理盐水0.32ml/kg。在实验的第4、8和12周分别对实验组和对照组的股骨头行微血管墨汁灌注,研究股骨头MVD的变化;制作半薄切片,在透射电镜下分别观察实验组和对照组的股骨头组织细胞的超微结构。拍摄兔耳背微血管网观察用药前后的变化。结果实验组双侧股骨头松质骨和密质骨的单位面积内MVD与对照组相比在用药3个月后明显下降(P<0.01)。兔耳背微血管网随用药时间的延长逐渐变稀疏。股骨头各系组织细胞内均发现有脂质堆积;骨细胞核膜失去连续性、碎裂,染色质溶解;血管内皮细胞内出现脂滴,胞膜结构不完整,可见明显的裂隙,线粒体肿胀、变圆,结构不清;脂肪细胞异常肥大,核内出现脂滴,并压迫小静脉,管腔变窄;小静脉内可见红细胞相互重叠呈“缗线状”。结论骨内压升高是激素性骨坏死病理过程中的一个表现,与肥大的脂肪细胞压迫小静脉有关。长期大剂量使用糖皮质激素可抑制

Mechanism of femoral head necrosis induced by long term glucocorticoid treatment in rabbit model

Objective To explore the mechanism of the femoral head necrosis induced with long term glucocorticoid treatment by means of microvascular density and cellular ultrastructure. Methods 40 Japanese rabbits were used to establish an animal model of the femoral head necrosis induced by long term glucocorticoid treatment using injection with methylprednisolone 8 mg/kg weekly. In studying cellular ultrastructure and microvascular density of the femoral head necrosis models, the slides were made after vascular infusion with Chinese ink on 4th, 8th, and 12th week of the experiment. The network of microvasculature of the rabbit ear was photographied as a reference data before and after methylprednisolone treatment. Results Microvascular density in bilateral cancellous and compact bone of the femoral head became decreased statistically after 12 weeks of glucocorticoid treatment(P< 0.01). Microvascular density of the rabbit ear became gradually less along with the treatment. Fatty degeneration was discovered in each kind cell of the femoral head. Pyknosis, karyorrhexis, karyolysis of the osteocytes were easily found. Nuclear membrane of the osteocyte was interrupted. There was also liposomes in vascular endothelia whose mitochondria became swollen. The structure of the mitochondria could not be seen clearly, the membrane was discontinous ,the rupture of endothelial membrane was observed. The adipocyte became very large and compressed venular canal which became very narrow. The RBC was closely sticked together as a thread of coins. Conclusion High intraosseous pressure was possiblly caused by the huge adipocyte which compressing the microvein of the marrow. Long-term glucocorticoid treatment inhibited the growth and proliferation of capillary and fasted degradation and closing the capillary, so that microvascular density became decresing. Finally there was no enough blood supply for femoral head after long term glucocorticoid treatment, so all kind cells were brought about of degeneration and up to the femoral head necrosis.