NEL样1型基因联合唑来膦酸预防股骨头坏死塌陷作用的初步观察

Combined Effects of NEL-like Type 1 Gene and Zoledronate in Preventing Collapse of the Femoral Head

目的观察NEL样1型基因(NELL-1)联合唑来膦酸用于股骨头坏死治疗是否可以预防股骨头的塌陷,并促进新骨形成。方法雄性SD大鼠24只,随机分为3组:假手术组、安慰剂组和NELL-1唑来膦酸联合治疗组。假手术组为正常对照组,安慰剂组在建立股骨头坏死模型后给予生理盐水治疗,NELL-1唑来膦酸联合治疗组在建立股骨头坏死模型后给予NELL-1髋关节注射并联合唑来膦酸皮下注射治疗。术后5周处死,取术侧股骨分别行X光照相,显微CT和组织学检查。结果大体观察NELL-1唑来膦酸联合治疗组可见股骨头形态良好,安慰剂组可见股骨头轻度变扁。各组均未观察到异位成骨现象。X光照相检查NELL-1唑来膦酸联合治疗组股骨头高度与宽度比值明显高于安慰剂组(P<0.01),而与假手术组差异无统计学意义(P>0.05)。显微CT检查显示3组间股骨头的体积、股骨头内骨量、股骨头骨矿盐含量NELL-1唑来膦酸联合治疗组和假手术组相比差异无统计学意义(P>0.05),但都大于安慰剂组(P<0.01)。组织学检查显示NELL-1唑来膦酸联合治疗组股骨头内以活骨为主,与安慰剂组相比,存在活跃的成骨细胞活动而破骨细胞数则明显减小。结论 NELL-1联合唑来膦酸用于大鼠的创伤性骨坏死治疗,可以促进成骨细胞活动,抑制破骨细胞活动,保存骨量和股骨头形态,具有良好的预防股骨头坏死塌陷的作用,有望实现骨坏死病程的逆转。

Objective To determine if combined therapy consisting of NEL-like type 1 gene （NELL- 1 ） and zoledronate can prevent the collapse of the femoral head and stimulate the new bone formation in an animal model of osteonecrosis. Methods Ischemic osteonecrosis was surgically induced in 24 SD rats, whicih were e- qually randomly divided into three groups： combination group, treated with both NELL-1 and zoledronate; sham operation group; and placebo group, treated with normal saline solution. The animals were killed 5 weeks after surgery. Radiography, MicroCT, histology, and immunohistochemistry were performed to analyze the re- suits. Results Morphologically, the femoral head was at good shape in the combination group, while mildly flattened femoral head was seen in the placebo group. No heterotopic ossifications were observed in each group. MicroCT assessment showed significantly higher total and bone mineral volume in the combination group than in the placebo group （ P 〈 0. 01 ）, whereas no such significant difference was found when compared with the sham operation group （P 〉 0. 05 ）. Histological assessment showed more active osteoblast activity and reduced os- teoclast activity in the combination group compared with placebo group. Conclusion A combination of NELL-1 and zoledronate can decrease the femoral head deformity while stimulating bone formation in a traumatic rat osteo- necrois model, showing a potential to reverse the osteonecrosis.