骨形态发生蛋白-7复合纤维蛋白对大鼠骨质疏松性椎体骨折愈合的影响

Complex of bone morphogenetic protein 7 and fibrin protein on the healing of osteoporotic vertebral fracture

目的:观察以纤维蛋白为载体的骨形态发生蛋白-7(BMP-7)对骨质疏松性椎体骨折愈合的影响,探讨局部应用BMP-7纤维蛋白复合物治疗骨质疏松性椎体骨折的可行性。方法:雌性SPF级8月龄SD大鼠54只,随机选取36只,经去除卵巢建立骨质疏松模型并随机分为A、B组,每组18只;另18只行伪手术,在背部卵巢周围切除等体积脂肪,作为对照组(C组)。术后3个月所有动物采用L5椎体手术开窗刮除术区内松质骨方法建立骨折模型,A组骨折区内放入含BMP-724μg和纤维蛋白20mg的凝胶状混合物,B组和C组于同部位放入等体积小牛血清,盖好窗口骨瓣。建立骨折模型后4、6、8周,每组处死动物3只,取L5椎体切片行HE染色;6、8、12周时每组处死动物3只,行L5椎体力学性能测试(载荷能力、弹性模量和最大应变量)。结果:骨折后4周3组骨折区均有纤维骨痂形成,但B组纤维骨痂量少于A、C组;6周时A、C组有较多骨性骨痂形成,B组仅有微量骨性骨痂;8周时A、C组均为成熟小梁骨,骨折基本愈合,B组骨性骨痂量少,仍以纤维骨痂为主,尚有部分骨缺损存在;各时间点A组与C组相似。骨折后6、8、12周A、C组L5椎体的最大载荷、弹性模量及8、12周时的最大应变量均明显高于B组(P<0.05或0.01),B组6周时的最大应变量与A、C组比较无显著性差异(P>0.05),各时间点A组与C组比较无显著性差异(P>0.05)。结论:局部应用以纤维蛋白为载体的BMP-7能明显促进大鼠骨质疏松性椎体骨折的愈合,纤维蛋白可作为BMP-7的载体。

Objective：To investigate the effect and feasibility of local usage of complex of bone morphogenetic protein 7 and fibrin protein on the healing of osteoporotic vertebral fracture.Method：36 female SPF SD rats of 8 months old were subjective to ovary resection to establish osteoporotic model and were divided into group A and B randomly with each group of 18 animals,and other 18 animals experiencing the sham operation with only fat tissue dissection were regarded as control group（group C）.L5 laminectomy was performed on all animals after 3 months to establish the fracture model.24μg BMP and 20mg fibrin gelatin mixture was placed in group A,while same volume of calf serum in group B and C.3 animals in each group were sacrificed at 4,6 and 8 week respectively and L5 vertebral samples were harvested for immunohistochemical test.3 animals in each group were sacrificed at 6,8 and 12 week respectively to perform L5 vertebral biomechanical test（load,module and maximum strain）.Result：Fibrous bone scar formation was evidenced in all groups at 4 week with group B less than group A and C;at 6 week more osseous formation was evidenced in group A and C than in group B which had only little bone formation;at 8 week mature trabecula formation was evidenced in group A and C,while group B had mostly fibrous osseum and partial defect.Group A presented same characteristics with group C.The maximum load and module for L5 vertebra of group Aand C at 6,8 and 12 week was higher than in group B（P〈0.05 or 0.01）,the maximum strain at 6 week for group B and A,C showed no significant difference（P〉0.05）,and group A and C at each time point showed no significant difference（P〉0.05） either.Conclusions：Local usage of complex of bone morphogenetic protein 7 and fibrin protein can promote the healing of osteoporotic vertebral fracture and fibrin protein can be used as carrier.