不同剂量rhBMP2修复兔桡骨骨缺损的比较△

Comparison of different doses of rhBMP2 used for repairing radial bone defect in rabbit

摘要:

[目的] 利用兔桡骨临界骨缺损模型，研究不同剂量的重组人骨发生蛋白 2 （recombinant human bone morphogenetic protein-2, rhBMP-2）对骨缺损修复的量效关系。[方法]将 36 只新西兰白兔建立单侧桡骨骨缺损模型，随机分为空白组、海绵空白组、自体骨组、低剂量组（0.25 mg rhBMP-2）、中剂量组（0.5 mg rhBMP-2）、高剂量组（2.5 mg rhBMP-2），每组 6 只。对骨缺损给予相应处理。分别于术后 4、8 周，行 X 线检查、MicroCT 检查和组织学观察评估。[结果]与术后第 4 周相比，8 周时各组 Lane Sandhu X 线评分均增加，其中，空白组和海绵空白组两个时间点间差异无统计学意义 （P＞0.05），而自体骨组、 低、中、高剂量组的两时间点间差异有统计学意义 （P＜0.05）。相应时间点，Lane Sandhu X 线评分由低至高均为空白组＜海绵空白组＜低剂量组＜自体骨组＜中剂量组＜高剂量组，差异有统计学意义 （P＜0.05）。与术后 4 周相比，8 周时 6 组 MicroCT 检测的骨矿密度 （bone mineral density, BMD） 和骨小梁数目 （trabecular number, Tb.N） 均增加，其中，低、中、高剂量组的两时间点间差异有统计学意义 （P＜0.05）。 相应时间点，BMD 和 Tb.N 均由低至高均为：低剂量组＜中剂量组＜高剂量组，差异有统计学意义（P＜0.05）。组织学观察表明，骨缺损新生骨的成熟度呈 rhBMP-2 剂量依赖性变化。[结论]在 0.25~2.5 mg 的剂量范围内，rhBMP-2 对兔桡骨临界骨缺损的骨修复效果呈剂量依赖性。

Abstract:

[Objective] To explore the dose-effect relationship of recombinant human morphogenetic protein-2 (rhBMP-2) in the criti- cal radius bone defect model in rabbit. [Methods] A total of 36 New Zealand white rabbits were randomly divided into blank group, sponge blank group, bone autograft group, low-dose group (0.25 mg rhBMP-2), medium-dose group (0.5 mg rhBMP-2) and high-dose group (2.5 mg rhBMP-2), with 6 rabbits in each group. After a 15 mm radius bone defect was made in rabbit, the corresponding bone defect treatments were conducted respectively. The X-ray check, Micro CT examination and histological observation were performed at 4 and 8 weeks postop- eratively. [Results] Compared with those 4 weeks after surgery, Lane Sandhu X-ray scores increased in all groups at 8 weeks, which were not significantly different between the two time points in the blank group and sponge blank group (P<0.05), while statistically significantly different in the bone autograft group, low, medium and high dose groups (P<0.05). At the corresponding time points, Lane Sandhu X-ray scores ranked from low to high all as: blank groupP<0.05).Regarding Micro CT assay, the bone mineral density (BMD)and trabecular number (Tb.N) increased in all the 6grorps at 8 weeks comparde with those at 4 weeks after surgery, which proved statistically singnificant between the two time points in the low-dose,medium-dose and high-dose grouups(P<0.05).At the corresponding time points,BMD and Tb.N ranked from low to high as:low dose groupP<0.05).In addition, the histological observation showde that the maturty of new bone was dose-dependent with rhBMP-2.[Conclusion] In the dose range of 0.25mg to 2.5mg, the bone repair outcome of rhBMP-2 in the critical radial bone defect is dose-dependent.