磷酸钙骨水泥复合辛伐他汀修复大段骨缺损实验研究

Experimental study of Calcium Phosphate cement combined Simvastatin in repairing large segmental bone defects

目的探讨磷酸钙骨水泥复合辛伐他汀修复大段骨缺损的可行性,为临床解决骨缺损修复难题提供理论依据。方法取新西兰大白兔24只,手术去除双侧桡骨中段15 mm骨质,制备骨缺损模型,将其随机分为对照组和实验组,每组各12只。对照组在双侧骨缺损区单纯植入磷酸钙骨水泥,实验组在双侧骨缺损区植入磷酸钙骨水泥和辛伐他汀复合物。分别在4、8、12周每组随机处死4只,取标本行肉眼观察、X线检查、骨密度测定,并制作病理切片,行新生骨量分析、组织形态学及免疫组化观察。结果肉眼观察及X线检查:实验组4、8、12周骨痂生长及骨质连续情况均优于对照组;骨密度:实验组4、8、12周骨密度均高于对照组,差异均有统计学意义(P<0.05或P<0.01);组织形态学观察:实验组成骨质量及速度优于对照组;新生骨定量分析:实验组4、8、12周新生骨面积百分比均高于对照组,差异均有高度统计学意义(P<0.01);免疫组化观察:实验组骨缺损区骨形态发生蛋白-2(BMP-2)广泛出现在未成熟骨细胞及成骨细胞胞浆中,可见棕黄色阳性染色,4周时最为明显,对照组阳性染色区域要弱于同期对照组。结论辛伐他汀具有成骨作用,局部植入磷酸钙骨水泥及辛伐他汀复合物可促进大段骨缺损区的修复。

Objective To evaluate the effect of Calcium Phosphate cement combined Simvastatin in repairing large segmental bone defects,and provide the basis for clinical treatment.Methods Twenty four New Zealand white rabbits with 15 mm radial critical size defects on both sides were randomized into experimental and control group,each group had 12 rabbits.The combination of Calcium Phosphate cement and Simvastatin was implanted on both sides in experimental group,and Calcium Phosphate cement was implanted on both sides in the control group.4 rabbits were killed randomly in each group to observe the fracture specimens at 4,8 and 12 weeks after the operation.General observation,X-ray inspection,bone mineral density （BMD） and pathological section were carried out to observe the new bone formation,histomorphology and immunohistochemistry.Results General observation and X-ray inspection：repair of bone defect performed better in experimental group than in control group at 4,8 and 12 weeks after operation.Bone mineral density：bone mineral density war were superior in experimental group at 4,8 and 12 weeks after operation than those in the control group,with significant statistical differences （P ＜ 0.05 or P ＜ 0.01）.Histomorphology observation：the bone quality and bone formation quantity in experimental group were much better than those in control group at 4,8 and 12 weeks after operation.Quantitative analysis of new bone：the percentages of new bone formation in the experimental group were higher than those in control group,with significant statistical differences （all P ＜ 0.01）.Immunohistochemical staining：the expression of BMP-2 appeared widely in the cytoplasm of immature bone cells and osteoblasts in experimental group,especially at 4 weeks.The positive staining areas in control group were lighter than those in experimental group at 4,8 and 12 weeks after operation.Conclusion Simvastatin can improve bone formation,local implantation of the combination of the Calcium Phosphate cement and Simvastatin can promote repairing large Segmental bone defects.