纤维蛋白为载体的BMP-4/7对骨质疏松性骨缺损愈合过程的影响

Effect of BMP-4/7 with Fibrin as Carrier on Healing Process of Osteoporotic Bone Defect

目的观察以纤维蛋白为载体的骨形态发生蛋白4/7(BMP-4/7)对骨质疏松性椎体骨缺损愈合中Ⅰ型骨胶原蛋白的影响,探讨局部应用BMP-4/7+纤维蛋白复合物治疗骨质疏松性椎体骨缺损的可行性。方法将84只大鼠依据随机数字法分为4组,每组21只。A组:骨质疏松性骨缺损+(BMP-4/7 24μg+纤维蛋白20 mg);B组:骨质疏松性骨缺损+胎牛血清;C组:正常骨质骨缺损+(BMP-4/7 24μg+纤维蛋白20 mg);D组:正常骨质骨缺损+胎牛血清。于骨缺损建模后1、2、4、5、8、12周采用免疫印迹法测定各组椎骨结痂中Ⅰ型骨胶原蛋白的含量;同时在4、8、12、16周检测骨密度和生物学力学特征,综合判断局部骨愈合情况。结果在4、5、8、12周时,B组和D组Ⅰ型骨胶原蛋白含量低于A组,C组均高于B组,D组低于C组(P <0. 05),A组与C组比较差异无统计学意义(P> 0. 05),D组高于B组(P <0. 05)。第8周、12周、16周时,B组和D组骨密度低于A组,C组高于B组,D组低于C组(P <0. 05),A组与C组比较差异无统计学意义(P> 0. 05),D组高于B组(P <0. 05)。第8周、12周、16周时,B组和D组的最大载荷量、最大应变力、弹性模量低于A组,C组均高于B组,D组低于C组(P <0. 05),A组与C组间比较差异无统计学意义(P> 0. 05),D组高于B组(P <0. 05)。A组、B组、C组和D组的Ⅰ型骨胶原蛋白含量与最大载荷量、最大应变量、弹性模量均呈正相关(P <0. 05)。结论局部应用以纤维蛋白为载体的BMP-4/7能明显增加大鼠骨质疏松性椎体骨缺损愈合过程中局部Ⅰ型骨胶原蛋白含量,改善局部骨质生物学性能。

Objective To observe the effect of bone morphogenetic protein 4/7( BMP-4/7) with fibrin as carrier on the expression of type Ⅰ collagen protein in healing of osteoporotic vertebral bone defect and to explore the feasibility of local application of BMP-4/7 and fibrin complex in the treatment. Methods A total of 84 rats were divided into 4 groups according to the random number method,21 rats each. Group A: osteoporotic bone defect +( BMP-4/7 24 μg + fibrin20 mg);group B: osteoporotic bone defect + fetal bovine serum;group C: normal bone defect +( BMP-4/7 24 μg + fibrin20 mg);group D: normal bone defect + fetal bovine serum. The immunoblotting was used to determine vertebrae scabby type Ⅰ collagen protein content after 1,2,4,5,8,12 weeks of establishing the bone defect models;meanwhile,the bone mineral density and biomechanical characteristics were measured at week 4,8,12 and 16 to comprehensively assess the local bone healing. Results At 4,5,8 and 12 weeks,the collagen content of type Ⅰ bone in group B and group D was lower than that of group A,and group C was higher than group B,group D was lower than group C( P < 0. 05),while there was no significant difference between group A and group C( P > 0. 05),group D higher than group B( P < 0. 05). At the 8 th week,12 th week and 16 th week,the bone mineral density in group B and group D was lower than that in group A,group C was higher than that in group B,and group D was lower than that in group C( P < 0. 05),while there was no significant difference between group A and group C( P > 0. 05),group D higher than group B( P < 0. 05). At the 8 th week,12 th week and 16 th week,the maximum load,maximum strain force and elastic modulus of group B and group D were lower than those of group A,group C higher than group B,and group D lower than group C( P < 0. 05),while there was no significant difference between group A and group C( P > 0. 05),group D higher than group B( P < 0. 05). There was a positive correlation between type I bone collagen content and maximum load,maximum strain and elastic modulus in group A,group B,group C and group D( P < 0. 05). Conclusion The local application of BMP-4/7 with fiber protein as the carrier can obviously increase the local type Ⅰcollagen protein content in osteoporotic vertebral body bone defect healing process,and improve the local bone biological performance of the rats.