慢病毒介导的骨形态发生蛋白-2治疗骨质疏松骨折的效果

The effect of lentivirus-mediated BMP-2 on the treatment of osteoporotic fractures

目的探讨慢病毒介导的骨形态发生蛋白-2(BMP-2)治疗骨质疏松骨折的效果。方法建立30只大鼠骨质疏松模型并进行分组。模型组和BMP-2治疗组(即BMP-2组)进一步制作左胫骨中段横行骨折模型,并于骨折当天在骨折局部分别皮下注射对照病毒和BMP-2质粒的慢病毒,而对照组不作骨折处理,只在相应部位皮下注射等体积的PBS。4d后分别处死各组3只大鼠,用Western blot检测骨折局部皮下BMP-2的表达情况;治疗8周后处死其余大鼠,取左胫骨进行X线检查并评分,测定骨密度及骨的生物力学指标,观察骨痂组织学变化。结果 BMP-2组大鼠骨折处皮下组织BMP-2蛋白表达水平明显高于对照组和模型组(P<0.05)。模型组和BMP-2组大鼠胫骨X线评分与对照组比较,明显降低(P<0.05),但是BMP-2组明显高于模型组(P<0.05)。模型组和BMP-2组大鼠骨密度明显低于对照组,而BMP-2组明显高于模型组(P<0.05)。模型组和BMP-2组大鼠胫骨3点弯曲参数(最大载荷、最大应力、破坏载荷和破坏应力)与对照组大鼠比较,均明显下降,而BMP-2组各参数较模型组明显升高(P<0.05)。骨痂组织HE染色显示,模型组大鼠软骨性骨痂较多,骨小梁较细,排列稀疏紊乱,而BMP-2组大鼠可见大量软骨性骨痂向骨性骨痂转变,新生形成大量编织骨小梁。结论慢病毒介导的BMP-2能促进骨形成,促进骨折部位愈合,对骨质疏松性骨折具有很好的治疗效果。

Objective To investigate the effect of lentivirus-mediated bone morphogenetic protein（BMP-2）on the treatment of osteoporotic fractures.Methods We divided 30 osteoporotic model rats into control group,model group and therapy group.The model group and therapy group were used to make the left tibial transverse fracture model.In the model group and the therapy group,rats were treated by local fracture subcutaneous injection of lentivirus which was packed with empty plasmid and BMP-2 plasmid.The rats in the control group were injected with PBS only.The three groups of rats were sacrificed at 8 weeks after operation,the expression of BMP-2 was used to analyze by Western blot.X-ray score,bone density,bone biomechanical index and bone structure were measured.Results Lentivirus-mediated BMP-2 gene was expressed in vivo.Compared with that in the control group,the X-ray score in the model group and the therapy group was lower（P〈0.05）.The X-ray score was significantly higher in the therapy group than in model group（P〈0.05）.The bone mineral density in the model group and the therapy group was significantly reduced compared with that in the control group,while bone mineral density in the therapy group significantly increased compared with that in the model group（P〈0.05）.Compared with the control group,the 3 point bending parameters（maximum load,maximum stress,failure load and failure stress）in the model group and the therapy group significantly decreased,while the 3 point bending parameters in the therapy group were significantly higher than those in the model group（P〈0.05）.HE staining showed that there was cartilage callus and the trabecular bone was thin and sparse in the model group,while a large amount of cartilage callus changed into the bony callus in the therapy group.Conclusion Lentivirus-mediated BMP-2 can promote bone formation and promote the healing of fracture site,which has a good therapeutic effect on osteoporotic fracture.