CAJ | 학술논문

背景: 重组人骨形态发生蛋白2作为一种新约已应用于临床.但在椎间盘内诱导成骨的研究报道很少.目的: 通过动物实验,观察重组人骨形态发生蛋白2埘兔椎体间融合的影响.设计、时间及地点: 随机对照动物实验多水平评估,于2003-02/07在肯岛大学医学院附属医院完成.材料: 24只纯种成年新西兰大白兔,体质量3.5-4.5 kg,分离暴露L4-5、L5-6椎间盘;重组人骨形态发生蛋白2,1 mg/支,纯度≥95%,无菌包装,购自北京市百灵克生物制品有限公司.方法: 24只大白兔随机投币法分为实验组和对照组,每组12只.实验组向L4-5椎间盘的髓核中产射含200 μg重组人骨形态发生蛋白2的生理盐水溶液20uL;向L5-6的髓核中注射等量的生理盐水作为自身对照;对照组动物L4-5椎间盘的髓核中注射生理盐水20 μL.主要观察指标: 术后10,30,60,90 d应用手法检杏、组织学和影像学观察注射节段的形态变化.结果: 纳入新西兰大白兔24只,均进入结果分析.①实验组10 d L4-5节段活动范围无明显变化;30 d活动范围轻度受限:60 d活动范围明显受限:90 d L4-5节段皆固定.作为自身对照的L5-6节段及对照组关节活动范围无明显变化.②实验组10 d L4-5椎体间隙变窄:90dL4-5椎间隙消失,椎体间形成骨性融合.对照组及作为自身对照的L5-6节段椎间隙透光度无明显改变.③实验组10 d髓核细胞逐渐变小,90 d部分软骨终板已转化为成熟的编织骨:纤维环的胶原纤维结构逐渐消失,10 d和30 d均可见大量间充质细胞在纤维环外围聚集;90 d纤维环靠近软骨终板处已形成成熟的编织骨.对照组各时间点组织学形态无明显变化.结论: 重组人骨形态发生蛋白2可诱导椎间盘成骨,达到椎体间融合的目的.
배경: 중조인골형태발생단백2작위일충신약이응용우림상.단재추간반내유도성골적연구보도흔소.목적: 통과동물실험,관찰중조인골형태발생단백2시토추체간융합적영향.설계、시간급지점: 수궤대조동물실험다수평평고,우2003-02/07재긍도대학의학원부속의원완성.재료: 24지순충성년신서란대백토,체질량3.5-4.5 kg,분리폭로L4-5、L5-6추간반;중조인골형태발생단백2,1 mg/지,순도≥95%,무균포장,구자북경시백령극생물제품유한공사.방법: 24지대백토수궤투폐법분위실험조화대조조,매조12지.실험조향L4-5추간반적수핵중산사함200 μg중조인골형태발생단백2적생리염수용액20uL;향L5-6적수핵중주사등량적생리염수작위자신대조;대조조동물L4-5추간반적수핵중주사생리염수20 μL.주요관찰지표: 술후10,30,60,90 d응용수법검행、조직학화영상학관찰주사절단적형태변화.결과: 납입신서란대백토24지,균진입결과분석.①실험조10 d L4-5절단활동범위무명현변화;30 d활동범위경도수한:60 d활동범위명현수한:90 d L4-5절단개고정.작위자신대조적L5-6절단급대조조관절활동범위무명현변화.②실험조10 d L4-5추체간극변착:90dL4-5추간극소실,추체간형성골성융합.대조조급작위자신대조적L5-6절단추간극투광도무명현개변.③실험조10 d수핵세포축점변소,90 d부분연골종판이전화위성숙적편직골:섬유배적효원섬유결구축점소실,10 d화30 d균가견대량간충질세포재섬유배외위취집;90 d섬유배고근연골종판처이형성성숙적편직골.대조조각시간점조직학형태무명현변화.결론: 중조인골형태발생단백2가유도추간반성골,체도추체간융합적목적.
BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used on clinic; however, there are still few reports addressing rhBMP-2-induced osteogenesis in intervertebral disc.OBJECTIVE: To verify the effect of rhBMP-2 to induce interbody fusion in rabbits.DESIGN, TIME AND SETTING: Randomized controlled animal study and multi-level evaluation, which was performed in Affiliated Hospital of Medical College of Qingdao University from February to July 2007.MATERIALS: 24 adult New-Zealand rabbits weighing 3.5-4.5 kg were used to expose L4-5 and L5-6 intervertebral disc; rhBMP-2 (1 mg/ampoule, purity≥95%) was provided by Beijing Bailingke Biological Products Co., Ltd.METHODS: 24 rabbits were randomly divided into experimental group and control group with 12 rabbits for each. In the experimental group, saline (20 μL, containing 200 μg rhBMP-2) was injected into nucleus pulposus of L4-5 intervertebral disc; equivalent saline was inserted into nucleus pulposus of L5-6 intervertebral disc as controls. Rabbits in the control group were injected with saline (20 μL) into nucleus pulposus of L4-5 intervertebral disc.MAIN OUTCOME MEASURES: Morphological changes of injected segments were observed by hand-feeling check together with histological and imaging tests at 10, 30, 60, and 90 days postoperatively.RESULTS: 24 rabbits were included in the final analysis. ①In the experimental group, the motion range of L4-5 segment was not limited at 10 days postoperatively, and lightly limited at 30 days, but severely limited at 60 days postoperatively; L4-5 segment was fixed tightly at 90 days postoperatively. Moreover, motion range of L5-6,segment and articular motion range in the control group were not changed remarkably. ② L4-5 interbedy space was narrowed at 10 days or even disappeared at 90 days postoperatively, and then osteogenesis fusion was formed. Transmittance of intervertebral space in the L5-6 segment and in the control group was not changed obviously. ③ Nucleus pulposus was gradually shrunk at 10 days postoperatively; partial cartilage endplate transformed into mature woven bone, and collagen fiber structure of annulus fibrosus gradually disappeared at 90 days postoperatively. A lot of mesenchymal cells were aggregated surrounding annulus fibrosus at 10 and 30 days postoperatively. Moreover, mature woven bone was formed in annulus fibrosus near to cartilage endplate at 90 days postoperatively. However, histological and morphological changes were not found in the control group at those four time points.CONCLUSION: rhBMP-2 can induce intervertebral disc osteogenesis so as to achieve interbody fusion.