【摘要】 目的 建立兔激素性股骨头坏死模型，探讨其可能的发病机制。方法 用改进的马血清加甲强龙的方法诱导制备兔激素性股骨头坏死动物模型，通过X线检查及组织病理学方法观察坏死模型建立情况；采用免疫组化方法检测造模后2、4、8周兔股骨头内过氧化物酶体增殖体激活受体γ(PPARγ)及骨形态发生蛋白2(BMP2)的局部表达情况。结果 模型组双侧股骨头内骨质密度不均一，关节面模糊；骨小梁稀疏变细、断裂，骨小梁骨细胞空骨陷窝明显增多，脂肪细胞体积增大，数目增多，骨髓腔内造血组织明显减少。造模后2、4、8周时，模型组动物股骨头内PPARγ表达逐渐增强；BMP2在2周时呈阳性染色，4、8周时转阴性。结论 用改进的马血清加甲强龙的方法诱导制备兔激素性股骨头坏死动物模型，其病理变化及影像学改变符合临床典型的股骨头坏死的特征；激素性股骨头坏死的发生可能与PPARγ表达增强、BMP2表达减弱有关。
【关键词】 激素性股骨头坏死；动物模型；免疫组织化学；过氧化物酶体增殖体激活受体－γ；骨形态发生蛋白－2
Construction of the model of steroidinduced osteonecrosis in rabbits and exploration of the pathogenesis of the osteonecrosis femoral head
ABSTRACT: Objective To construct the model of steroidinduced osteonecrosis in rabbits and explore the pathogenesis of osteonecrosis femoral head. Methods We constructed the rabbit model of femoral head necrosis with the modified method of horse serum plus methylprednisolone. The osteonecrosis model was evaluated by Xray photograph and hematoxylin and eosin stain; immunohistochemistry was performed to detect the dynamics of the PPARγ and BMP2 expressions inside the femoral head of steroidinduced osteonecrosis in rabbits. Results Xray photograph showed that the femoral head was inhomogeneous in model group. In model group, there were increased numbers of empty bone lacunae and larger fat cells, decreased hematopoietic tissues compared with normal control group under light microscopy and histological staining. The expression of the PPARγ in model group at the 2th, 4th and 8th week was obviously higher than that of control group. Its expression had an upgrade tendency, with the longer time. The expression of BMP2 in model group was extremely lower than that in control group at the 2nd week. In 4th and 8th week, there was no expression of the BMP2 in model group. Conclusion The typical animal model of osteonecrosis is induced by the modified method of horse serum plus methylprednisolone. Inside the femoral head of steroidinduced osteonecrosis in rabbits, the expression of the PPARγ is upgraded; the expression of the BMP2 is inhibited.
KEY WORDS: femoral head necrosis; peroxisome proliferatoractived receptorgamma; bone morphogenetic protein2; animal model; immunohistochemsitry
股骨头缺血性坏死是临床常见的难治性疾病之一，其发病原因众多，发病机理尚不明确。该病临床上分为创伤性与非创伤性两大类，其中激素性股骨头坏死在非创伤性股骨头坏死中发病率居首位，并呈逐年增高的趋势。针对激素性股骨头坏死的原因学研究，国内外学者提出了多种假说，但迄今尚无一种学说可以完全解释其发病机理。建立激素性股骨头坏死动物模型时间长、成本大、成功率低、动物死亡率高，因此对造模方法的研究仍将是长期面临的一项课题。在本研究中我们通过对已有造模方法进行改进，试图寻找一种新的效率更高的造模方法，并在此基础上对激素性股骨头坏死的发病机理进行了进一步的探讨。
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