大鼠脊柱融合模型中BBP增强BMP-2的骨诱导作用

Adjunctive effect of a binding peptide on bone morphogenetic protein enhanced bone heal in a rodent spinal fusion model

[目的]验证在大鼠脊柱融合模型中BBP对于rhBMP-2骨诱导作用的影响。[方法]采取Lewis大鼠的脊柱后外侧横突间融合模型,在胶原海绵为载体的rhBMP-2中加入BBP并减少rhBMP-2的用量,测试两种不同剂量的BBP(500 ug和1 000 ug)有或无低剂量的rhBMP2(1 ug)时的骨融合效果,并与单纯的低剂量rhBMP-2(1 ug)组相对比。融合效果采用手工评估,影像学评分,Micro-CT评估和组织学评估4种方法。[结果]BBP本身不管是低剂量还是高剂量均不能诱导骨融合。BBP复合低剂量BMP-2不能完全取得与高剂量BMP-2完全相同的效果,但可以减少BMP-2的用量。加入BBP的低剂量BMP-2组显然较低剂量BMP-2组融合率高,而且与高剂量BMP-2组的融合率相近,而且BBP的低剂量BMP-2组显然较低剂量BMP-2组融合的要早。[结论]在大鼠的脊柱融合模型中,BBP本身不管是低剂量还是高剂量均不能诱导骨融合。BBP可以增强BMP-2的骨形成作用,提高融合率,降低BMP-2的使用剂量以及减少了剂量相关性副作用的发生率,但不能取得与高剂量BMP-2完全相同的效果。BBP可以减少脊柱融合所需的时间和提高形成骨的质量。进一步的研究可以优化BBP和BMP-2的剂量,从而为以后的临床手术应用中取得更好的融合效果。

[ Objective] A prospective 8 -week interventional trial employing a rat model of spinal fusion was made to test the effect on bone morphogenetic protein binding peptide （BBP） on rhBMP -2 induced bone healing. [ Methods] Posterolateral intertransverse process spinal fusion at L4,5 was performed in Lewis rats. Two doses of BBP （500 ug, and 1 000 rag） were tested with or without ＂low dose＂ （1 ug） rhBMP- 2 and the results were compared with the low dose （1 ug） rhBMP -2. Fusion was evaluated by radiology, histology, and manual palpation tests. [ Results ] Radiology revealed significant earlier fusion with 1 000 mg BBP and 1 ug BMP -2 combination when compared with low dose BMP -2 （1 ug） only （P 〈0.05） . Manual palpation and histology at eighth week revealed higher rate of fusion with the same combination with a nearly significant difference （P = 0. 057） . [ Conclusion ] Specific growth factor binding agents, such as BBP, can be compounded into carriers used in fusion procedures to decrease the dosage of BMP and possiblely decrease the side effects which are most likely.