采用激素联合内毒素建立兔中期股骨头坏死模型  

Medium stage femoral head osteonecrosis model in rabbits induced by a combination of popolysaccharide and methylprednisolone

作　　者：黄思俊[1] 白志强[2] 张弛[1] 刘伟[1] 傅光涛 李长川[1] 张彦[1] 李仕勋 丁悦[1] 

机构地区：[1]中山大学孙逸仙纪念医院骨外科,广州510000 [2]中山大学孙逸仙纪念医院放射科,广州510000

出　　处：《中华关节外科杂志（电子版）》2016年第3期79-84,共6页Chinese Journal of Joint Surgery(Electronic Edition)

摘　　要：目的探索激素联合内毒素建立兔股骨头坏死（ONFH）国际骨循环研究会（ARCO）中期（Ⅱb~Ⅲb期）模型的最佳时间,为进一步研究治疗中期ONFH提供动物模型。方法将周龄为28周的健康成年新西兰白兔36只雌雄各半,用单纯随机抽样法分为实验组（n=30）,对照组（n=6）。实验组予耳缘静脉注射1次低剂量的脂多糖（LPS）后,以24 h为间隔给予肌肉注射3次高剂量的甲基强的松龙（MPS）。对照组与实验组相同时间点注射等量生理盐水。于注射前及注射后4~9周行MRI检查,观察股骨头影像学改变,并通过病理切片明确ONFH改变。根据MRI检查结果,算出各周ARCO中期ONFH的发生率,卡方检验分析统计学差异。结果实验组动物注射MPS与LPS后出现3只动物死亡,B组则无死亡。注射后实验组股骨头ARCO中期坏死率：第4周为22.2%,第5周为57.4%,第6周为75.9%,第7周68.5%,第8周42.6%,第9周20.3%。对照组股骨头MRI信号未见异常。实验组第6周的ARCO中期ONFH率与第4、8、9周比较,差异均有统计学意义（P〈0.01）;出现ARCO中期ONFH的股骨头在光镜下表现为：空骨陷窝,骨小梁塌陷断裂,微血管的分布密度减少。结论用MPS联合LPS造模的ONFH发生率高,死亡率较低,是较好的非创伤性模型。本实验中ARCO中期发生率在第5~7周期间最高。Objective To explore the suitable time for establishing a stable animal model for osteonecrosis of femoral head（ ONFH） induced by a combination of endotoxin and glucocorticoid in rabbits with Association Research Circulation Osseous（ ARCO） grade Ⅱ b- Ⅲ b,so as to support the further research of treating the medium stage ONFH. Methods Thirty-six adult,half males and half females,New Zealand rabbits were randomly divided into two groups. Thirty of them were injected low-does lipopolysaccharide by ear-vein,following three gluteal injections of high dose methylprednisolone at 24 h intervals（ group A）; the other six rabbits were treated with a normal saline at the same time as a control（ group B）. MR imaging was performed before the first injection of lipopolysaccharide or methylprednisolone, and in the 4thto 9thweek after the last injection of lipopolysaccharide or methylprednisolone. The changes of the femoral head were observed,and the ONFH was confirmed by histology. According to the MR imaging appearance of the femoral head in the two groups,the incidence of osteonecrosis in ARCO grade Ⅱ b-Ⅲ b of each group was calculated and compared by Chi-squared test.Results Three animals died in group A after the last injection,while no animal died in group B. The rate of ARCO medium stage was 22. 2% in the 4thweek,57. 4% in the 5thweek,75. 9% in the 6thweeks,68. 5% in the 7thweek,42. 6% in the 8thweek,and 20. 3% in the 9thweek. MR imaging was ON negative in group B. Comparing the rate of ARCO mid-stage ONFH in group A in the 6thweek with that in the 4th,8thand 9thweek after the injection,there were statistically differences（ P〈0. 01）. The femoral head of osteonecrosis in ARCO mid-stage which was observed by light microscope showed empty lacunae,and thin even broken trabecular bone. Conclusion Methylprednisolone combining lipopolysaccharide can induce typical non-traumatic rabbit model,for its high ONFH incidence and low mortality. In this experiment,the highest incidence of ONFH in ARCO medium

关 键 词：股骨头坏死 骨坏死 内毒素类 甲泼尼龙 模型 动物 

分 类 号：R681.8[医药卫生—骨科学]