“手风琴”技术与去铁胺促进牵张成骨区骨再生效果的实验研究  

Effect of accordion technique and deferoxamine on promoting bone regeneration in distraction osteogenesis

作　　者：刘凯 史凌云[2] 王苏龙 艾尼孜尔·亚力坤 伊木让·哈米提 艾合买提江·玉素甫[1,3] LIU Kai;SHI Lingyun;WANG Sulong;Ainizier·Yalikun;Yimurang·Hamiti;Aihemaitijiang·Yusufu(Department of Trauma and Microreconstructive Surgery,the First Affiliated Hospital of Xinjiang Medical University,Urumqi Xinjiang,830054,P.R.China;Department of Orthopaedic Surgery,the First Affiliated Hospital of Xinjiang Medical University,Urumqi Xinjiang,830054,P.R.China;Xinjiang Key Laboratory of Trauma Repair and Reconstruction,Urumqi Xinjiang,830054,P.R.China)

机构地区：[1]新疆医科大学第一附属医院骨科中心显微修复外科,乌鲁木齐830054 [2]新疆医科大学第一附属医院骨科,乌鲁木齐830054 [3]新疆创伤修复重建重点实验室,乌鲁木齐830054

出　　处：《中国修复重建外科杂志》2024年第8期1001-1009,共9页Chinese Journal of Reparative and Reconstructive Surgery

基　　金：中央引导地方科技发展资金资助项目(ZYYD2022A03);科技创新领军人才项目(2022196274)。

摘　　要：目的比较牵张成骨(distraction osteogenesis,DO)矿化期给予牵张区灌注低氧诱导药物去铁胺(deferoxamine,DFO)和“手风琴”技术(accordion technique,AT)循环应力,激活缺氧诱导因子1α(hypoxiainducible factor 1α,HIF-1α)/VEGF信号通路,促进骨再生与重建的效果。方法取45只SPF级成年雄性SD大鼠,随机分为对照组、DFO组及AT组,每组15只。首先,所有大鼠截骨建立右侧股骨DO模型,截骨5 d后开始持续牵拉延长10 d;牵张完成后在矿化期内,对照组不作干预,DFO组于矿化第3周开始牵张区局部灌注DFO,AT组于矿化第3周开始给予循环应力刺激。观察各组大鼠一般情况;于牵张期结束及矿化第2、4、6周摄X线片,观察牵张区钙化情况;矿化第4、6周,取外周血行ELISA检测HIF-1α、VEGF、CD31及成骨相关转录因子(Osterix)表达,取股骨标本行大体观察以及组织学(HE染色)及免疫组织化学染色[HIF-1α、VEGF、骨桥蛋白(osteopontin,OPN)、骨钙素(osteocalcin,OCN)]观测;矿化第6周,取股骨标本行Micro-CT扫描,观测牵张区新生骨骨密度(bone mineral density,BMD)、骨体积/组织体积(bone volume/tissue volume,BV/TV)、骨小梁疏密度(trabecular separation,Tb.Sp)、骨小梁数量(trabecular number,Tb.N)及骨小梁厚度(trabecular thickness,Tb.Th),以及生物力学测试极限载荷、弹性模量、断裂能量及刚度,检测牵张区骨再生情况。结果术后3组大鼠均存活至实验完成。ELISA检测示,矿化第4、6周AT组血清中HIF-1α、VEGF、CD31及Osterix含量均高于DFO组和对照组(P<0.05)。大体观察、X线片、Micro-CT及生物力学试验示,DFO组和AT组股骨牵张区内骨形成显著优于对照组,且AT组髓腔实现完全再通,AT组牵张区新生骨BMD、BV/TV、Tb.Sp、Tb.N、Tb.Th以及极限载荷、弹性模量、断裂能量、刚度均优于DFO组、对照组,差异有统计学意义(P<0.05)。HE染色示AT组牵张区骨小梁形成、成熟程度优于DFO组、对照组。免疫组织�Objective To compare the effects of hypoxia-inducible drugs using deferoxamine(DFO)and accordion technique(AT)on activating the hypoxia-inducible factor 1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway to promote bone regeneration and remodelling during consolidation phase of distraction osteogenesis(DO).Methods Forty-five specific-pathogen-free adult male Sprague-Dawley(SD)rats were randomly divided into the control group,DFO group,and AT group,with 15 rats in each group.All rats underwent osteotomy to establish a right femur DO model.Then,continuous distraction was started for 10 days after 5 days of latency in each group.During the consolidation phase after distraction,no intervention was performed in the control group;DFO was locally perfused into the distraction area in the DFO group starting at the 3rd week of consolidation phase;cyclic stress stimulation was given in the AT group starting at the 3rd week of consolidation phase.The general condition of rats in each group was observed.X-ray films were conducted at the end of the distraction phase and at the 2nd,4th,and 6th weeks of the consolidation phase to observe the calcification in the distraction area.At the 4th and 6th weeks of the consolidation phase,peripheral blood was taken for ELISA detection(HIF-1α,VEGF,CD31,and Osterix),femoral specimens were harvested for gross observation,histological staining(HE staining),and immunohistochemical staining[HIF-1α,VEGF,osteopontin(OPN),osteocalcin(OCN)].At the 6th week of the consolidation phase,Micro-CT was used to observe the new bone mineral density(BMD),bone volume/tissue volume(BV/TV),trabecular separation(Tb.Sp),trabecular number(Tb.N),and trabecular thickness(Tb.Th)in the distraction area,and biomechanical test(ultimate load,elastic modulus,energy to failure,and stiffness)to detect bone regeneration in the distraction area.Results The rats in all groups survived until the termination of the experiment.ELISA showed that the contents of HIF-1α,VEGF,CD31,and Osterix in the serum of

关 键 词：牵张成骨 骨再生 骨重建 “手风琴”技术 低氧诱导药物 大鼠 

分 类 号：R687.3[医药卫生—骨科学]