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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 optimal time for the establishment of metaphase Ⅱ (Ⅱb ~ Ⅲb) rabbit model of osteonecrosis of the femoral head (ONFH) by the combination of hormones and endotoxin, and to provide an animal model for the further study of ONFH in the mid - term of treatment. Methods Thirty-six healthy adult New Zealand white rabbits of 28 weeks old were randomly divided into experimental group (n = 30) and control group (n = 6). In the experimental group, a low dose of lipopolysaccharide (LPS) was injected into the auricular vein to give intramuscular 3 doses of methylprednisolone (MPS) intramuscularly at 24 h intervals. Control group and experimental group at the same time point injection of saline. Before injection and 4 to 9 weeks after injection, MRI examination was performed to observe the imaging changes of the femoral head and confirm the change of ONFH by pathological section. According to the results of MRI examination, we calculated the incidence of ONFH mid-term ARCO in each week, and the Chi-square test analyzed the statistical differences. Results Three animals died after injection of MPS and LPS in experimental group, but no death in group B. Median necrosis rates of ARCO in experimental group were 22.2% in the fourth week, 57.4% in the fifth week, 75.9% in the sixth week, 68.5% in the seventh week, 42.6% in the eighth week and 20.3% in the ninth week. The control group femoral head MRI signal no abnormalities. The median ARF in the sixth week of the experimental group was significantly higher than that of the fourth, eighth, eighth, and eighth weeks (P <0.01). The femoral head of the ARCO metaphase ONFH under light microscope showed that the empty bone lacuna , Trabecular collapse collapse, the distribution of microvessels density decreased. Conclusion The incidence of ONFH with MPS combined with LPS is high and mortality is low, which is a good noninvasive model. The mid-term incidence of ARCO in this experiment during the first 5 to 7 weeks the highest.