甲基强的松龙冲击疗法引发股骨头缺血性坏死的实验研究

Experimental stuty of femoral head necrosis induced by stosstherapy with Solu-Medrol^TM

目的探讨急性应激时甲基强的松龙冲击给药对家兔骨与关节损伤的发生与发展机制，为早期干预治疗提供科学依据。方法优选健康新西兰家兔180只，随机分成6组：低剂量组、中剂量组、高剂量组、内毒素激素组、模型组和对照组。动态观察24周，隔周取材，动态观察生命体征变化、骨关节MRI、组织学改变、骨组织形态计量学及生物力学改变。结果内毒素激素组在给药2d死亡率高达35％，明显高于其他各组。MRI观察发现，除内毒素激素组外，其他各组双侧肱骨头和股骨头均未见明显异常信号改变，而内毒素激素组2周于T1加权像上出现股骨头或肱骨头骨髓异常低信号影，发生率40％。组织细胞学改变显示髓腔早期出现的脂肪变性，发展到脂肪细胞坏死、髓腔造血细胞退变、骨陷窝空虚、空骨陷窝增多、骨细胞坏死、微小血管阻塞。单纯激素各组多见脂肪性变。四环素荧光标记和Von Kossa染色显示明显的骨质疏松表现，内毒素激素组表现最为明显。结构力学和材料力学参数明显降低，激素组力学参数与激素用量呈负相关。结论甲基强的松龙冲击疗法可直接引发骨质疏松，骨质疏松的程度与用药量和给药方式相关。单纯甲基强的松龙冲击给药不能直接引发股骨头坏死。在内毒素作用下，实施大剂量甲基强的松龙冲击给药，可直接引发骨坏死。骨坏死发生与内毒素相关。甲基强的松龙引发的骨与关节损伤可防治，早期使用脂质清除剂和活血化瘀药可以干预骨坏死的进程。适时调控骨代谢可以预防骨质疏松。

Investigate the initial and developmental mechanism of rabbits bone and joint injuries induced by stosstherapy with Solu-Medrol TM. Methods 180 healthy Newzealand rabits were randomly divided into 6 groups, including low dosage; medium dosage; high dosage; endotoxin with Solu-Medrol^TM; model and control groups. The experiment totally lasted for 24 weeks. The samples were harvested every two weeks and the followed aspects were observed： vital sign, MR image of bones and joints, histomorphology, bone morphometryand vitodynamics. Results The mortality rate of endotoxin group was 35% after 2 d, significantly higher than the other groups. There was abnormal lower signal at humeral heads or femoral heads in endotoxin group during MR scan, but without obvious signal change in the other groups. A series of changes in histomorphology could be seen： adipocyte breeding, overlapping and dying, hematopoietic celof bone marrow degenerating, bone lacuna becoming hollow, osteocytenecrosis and microcirculation blockaged. Fatty change was found in the groups only with Solu-MedrolTM. The reticulate structure disappeared. The parameters of architectonic mechanics and material mechanics degraded significantly. The mechanic parameters in groups with Solu-MedrolTM had negative correlation with the dosage of SoluMedrolTM. Conclusion The stosstherapy with Solu-MedrolTM can directly induce osteoporosis, which relates to the dosage and way of Solu-MedrolTM. The stosstherapy associated with an attack of endotoxin can directly induce bone necrosis, but only Solu-MedrolTM can＇t. The injuries of bones and joints induced by SoluMedrolTM can be prevented and healed. The lipid scavenger and the drugs can promote blood flow and remove blood stasis, and intervene the proceeding of bone necrosis in early stage. Furtherly, the osteoporosis can be prevented by appropriately regulating bone metabolism.