【摘要】 目的 比较不同基因型I型神经纤维瘤病（NF1）小鼠椎体骨量减少并脊柱畸形的特征。方法 培育基因型WT、Nf1^+/-、Nf1^flox/flox;Col2.3Cre⁺、Nf1^flox/-;Col2.3Cre⁺小鼠并分组。其中，野生型WT小鼠为对照组。分别对各基因型小鼠进行X线、骨密度检测、外周定量CT扫描、破骨细胞与成骨细胞形态观察、生物力学分析、组织与细胞学检查。结果 通过双能X射线吸收测定（DXA）和外周定量计算机断层扫描（pQCT）,与对照组比较，Nf1^flox/-;Col2.3Cre⁺小鼠椎体高度、骨密度及骨量均显著减少。椎体形态学研究发现，Nf1^flox/-;Col2.3Cre⁺小鼠椎管面积（C）与椎体面积（V）比值明显增大。生物力学分析发现，Nf1^flox/-;Col2.3Cre⁺小鼠椎体峰值压力负荷和最大压强亦显著降低。组织与细胞学分析显示，Nf1^flox/-;Col2.3Cre⁺小鼠椎骨中破骨细胞数量显著增加，成骨细胞数量明显减少。结论 Nf1^flox/-;Col2.3Cre⁺小鼠表现出椎体骨量减少与脊柱结构功能异常，重现NF1患者营养不良性骨质疏松与畸形的脊柱特征性病理改变。为临床深入了解及治疗NF1致椎体骨质疏松及脊柱畸形提供科学依据。更多还原

【Abstract】 Objective To compare the characteristics of vertebral osteopenia and spinal deformity caused by different genotypes models of neurofibromatosis type 1（NF1）. Methods The WT, Nf1^+/-, Nf1^flox/flox; Col2.3 Cre⁺, and Nf1^flox/-;Col2.3 Cre⁺ mice were cultivated and divided into four groups. WT mice were used as control. Dual energy X-ray absorptiometry（DEXA） examination, bone mineral density detection, peripheral quantitative computed tomography（pQCT） scanning, morphological observation of osteoclasts, osteoblast culture, biomechanical analysis, and tissue and cytology were performed and compared among different genotypes of mice. Results Compared to those in the control group, the vertebral body height, bone mineral density and bone mass in Nf1^flox/-;Col2.3 Cre⁺ mice reduced significantly. The study of vertebral morphology found that the ratio of vertebral canal area（C） to vertebral body area（V） increased significantly in Nf1^flox/-;Col2.3 Cre⁺ mice. Biomechanical analysis found that the peak load and peak stress of vertebral body in Nf1^flox/-;Col2.3 Cre⁺ mice also decreased significantly. Tissue and cytological analysis showed that the number of osteoclasts increased and the number of osteoblasts decreased in the vertebrae of Nf1^flox/-;Col2.3 Cre⁺ mice. Conclusion The Nf1^flox/-;Col2.3 Cre⁺ mice show osteopenia and spinal structural and functional abnormalities. This mimics the characteristic changes of spine in NF1 patients with dystrophic osteoporosis. This study provides scientific basis for clinical understanding and treatment of osteoporosis and spinal deformity caused by NF1.更多还原