外源性神经生长因子促进大鼠牵张成骨区骨再生的研究  

Effect of exogenous β-nerve growth factor on bone regeneration in distraction area via rat models

作　　者：刘凯 王苏龙 任鹏[1] 艾合买提江·玉素甫[1] Liu Kai;Wang Sulong;Ren Peng;Aihemaitijiang Yusufu(Department of Trauma and Microreconstructive Surgery,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,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

出　　处：《中华实验外科杂志》2023年第7期1253-1257,共5页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目(82060401);中央引导地方科技发展资金资助项目ZYYD2022A03。

摘　　要：目的探讨牵张期给予牵张区持续灌注β神经生长因子(β-NGF)促进骨再生与重建的作用机制。方法2021年9月至2022年1月,选取由新疆医科大学实验动物中心提供健康成年雄性Sprague-Dawley(SD)大鼠40只,建立右侧股骨牵张成骨(DO)模型,并运用随机抽样法均分为A组(20例)和对照组(20例)。透视下牵张期给予对照组牵张区注射无菌0.9%生理盐水300μl,给予A组牵张区注射β-NGF(10μg/200μl)300μl。术后行X线、微型计算机断层扫描(micro-CT)、三点弯曲生物力学试验、血清标本酶联免疫吸附测定(ELISA)、骨组织学染色检测牵张区的骨再生情况。组间采用独立样本t检验或Mann-WhitneyU检验来评估。结果矿化第6周A组牵张区新生骨骨密度[(359.62±19.58)mm/cm^(3)比(278.41±25.73)mm/cm^(3),t=3.824,P<0.001]、骨体积/总组织体积[(43.83±2.48)%比(33.25±3.96)%,t=4.092,P<0.05]、极限载荷[(48.16±1.25)%比(27.35±2.68)%,t=4.045,P<0.05]、弹性模量[(58.93±2.57)%比(34.74±3.72)%,t=3.428,P<0.05]、断裂能量[(56.15±2.77)%比(29.26±3.68)%,t=6.503,P<0.05]及刚度[(52.68±3.86)%比(34.57±2.49)%,t=5.322,P<0.05]优于对照组。血清标本酶联免疫吸附测定及组织形态学分析结果显示牵张期给予牵张区持续灌注β-NGF有助于加速DO过程中骨再生与重建。结论牵张期给予牵张区持续灌注β-NGF可激活HIF信号通路,加速血管化成骨,有效促进骨再生与重建。Objective To evaluate the mechanism of bone regeneration and remodeling during distraction osteogenesis(DO)via continuous perfusion of exogenousβ-nerve growth factor(β-NGF)to the distraction area in a rat DO model.Methods From September 2021 to January 2022,40 healthy adult male Sprague-Dawley(SD)rats were provided by the Laboratory Animal Center of Xinjiang Medical University.A right femoral DO model was established and rats were randomly divided into group A(n=20)and control group(n=20).Under the fluoroscopy,300μL of sterile 0.9% saline was injected into the distraction area in the control group,and 300μL of β-NGF(10μg/200μL)was injected into the distraction area in group A.Postoperative X-ray,micro-computed tomography(micro-CT),three-point bending biomechanical testing,enzyme-linked immunosorbent assay of serum samples,and bone histological staining were performed to detect bone regeneration in the distraction area.Groups were assessed by independent sample t test or Mann-Whitney U test.Results At the 6th week of mineralization,the bone mineral density of new bone in the distraction area in group A[(359.62±19.58)mm/cm^(3) vs.(278.41±25.73)mm/cm^(3),t=3.824,P<0.05],bone volume/total tissue volume[(43.83±2.48%)vs.(33.25±3.96)%,t=4.092,P<0.05],ultimate load[(48.16±1.25)%vs.(27.35±2.68)%,t=4.045,P<0.05],elastic modulus[(58.93±2.57)%vs.(34.74±3.72)%,t=3.428,P<0.05],energy to fracture[(56.15±2.77)%vs.(29.26±3.68)%,t=6.503,P<0.05]and stiffness[(52.68±3.86)%vs.(34.57±2.49)%,t=5.322,P<0.05]were superior to the control group.The results of enzyme linked immunosorbent assay and histomorphological analysis showed that continuous perfusion of β-NGF in the distraction area during the distraction period helped to accelerate bone regeneration and remodeling.Conclusion Continuous infusion of β-NGF into the distraction area during distraction phase could activate the HIF signaling pathway,accelerate angiogenesis and osteogenesis,and effectively promote bone regeneration and remodeling.

关 键 词：神经生长因子 牵张成骨 骨再生 骨重建 动物模型 

分 类 号：R68[医药卫生—骨科学]