骨折局部应用伊班膦酸钠最适剂量选择的动物实验研究

A preliminary animal experimental study on the appropriate dose of ibandronate of for local application on fracture

目的:探讨局部应用不同剂量的伊班膦酸钠对兔骨折愈合过程的影响及最适剂量。方法:45只新西兰大白兔,按随机原则分为5组,建立兔桡骨骨折标准模型。对照组不予处理,其余各组通过局部途径分别给予0.1、0.2、0.3、0.4 ml伊班膦酸钠。于建模后1、2、4周行X线评分、骨生物力学测试,骨痂行病理学观察。结果:(1)X线观察结果:第2、4周时,局部用药各组评分均高于对照组(均P<0.05);0.3 ml组均高于0.1、0.2 ml组(均P<0.05),与0.4 ml组无显著统计学差异(均P>0.05)。(2)生物力学测试结果:第4周时,各局部用药组抗弯强度均高于对照组(均P<0.05);0.3 ml组均高于0.1、0.2 ml组(均P<0.05),与0.4 ml组无显著统计学差异(P>0.05)。(3)成骨细胞指数:局部用药各组在第1、2、4周均高于对照组(均P<0.05);第2、4周时,0.3 ml组均高于0.1、0.2 ml组(均P<0.05),与0.4 ml组无显著统计学差异(均P>0.05)。(4)免疫组化结果:局部用药组第1、2、4周血管内皮生长因子(VEGF)受体表达均高于对照组(均P<0.05);第2、4周时,0.3 ml组均高于0.1、0.2 ml组(均P<0.05),与0.4 ml组无显著统计学差异(均P>0.05)。结论:局部应用不同剂量的伊班膦酸钠均起到了促进骨折愈合的作用,其中以0.3 ml作用最显著,为本实验的最适剂量。

Objective： To explore the effects of different dose of ibandronate on fracture healing after local application and to select the best appropriate dose. Methods： Forty-five healthy New Zealand rabbits were randomly divided into five groups. All the rabbits were made into fracture healing model. Control group （CG） received no management. Each of different dose of ibandronate group was locally given 0.1, 0.2, 0.3, 0.4 ml different ihandronate. In week 1, 2, 4 the state of fracture healing were examined with DR scored, test through biomechanics pathological changes were observed in callus samples. Results： （ 1 ） Radiographic analysis ： in week 2, 4 the local application group obtained higher scores than in CG（ all P 〈 0.05 ）. The group of 0.3 ml obtained higher scores than 0.1, 0. 2 ml group（ all P 〈0.05）and had no difference compared with 0. 4 ml group（ all P 〉 0.05 ）. （2） Biomechanics test index： in week 4 anti-bending strength of the local application group was higher than in CG（all P 〈0.05）. The group of 0.3 ml had a higher index than 0.1, 0.2 ml group（ all P 〈0.05） and a similar one compared with 0.4 ml group （ P 〉 0.05 ）. （ 3 ） Osteoblastic index （OBI） ： in week 1, 2, 4, the local application group had a higher OBI than CG（ all P 〈0.05）. OBI in group of 0.3 ml was higher than in 0. 1,0.2 ml group （ all P 〈 0.05 ） and similar to that of 0.4 ml group （ all P 〉 0. 05 ）. （4） Immunohistochemistry results ： in week 1,2, 4 the receptor of VEGF expression of local application group was higher than that in CG（ all P 〈 0.05 ）. In week 2, 4, the group of 0.3 ml group expressed more than 0.1,0.2 ml group （ all P 〈 0.05 ） and showed no difference compared with 0.4 ml group （ all P 〉 0.05 ）. Conclusion： The local application for different dose of ibandronate has promotes healing of rabbits＇ fracture and 0.3 ml is the appropriate dose in the experimental study.