CAJ | 학술논문

目的探讨电穿孔介导的基因治疗对兔下颌骨牵引成骨过程中碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)表达的影响.方法新西兰大白兔双侧下颌骨截骨,术后3d开始以0.8 mm/d速度行下颌骨牵引,连续牵引7d,将实验动物分为:A、B、C、D、E5组.分别在牵引区注射2μg重组质粒pIRES-hVEGF165-hBMP2、pIRES-hBMP2、pIRES-hVEGF165、空质粒pIRES及生理盐水.各组实验动物均施加电穿孔刺激.各组分别于固定期第7、14、28天处死动物取材行免疫组织化学检查bFGF的表达,并利用病理图像分析系统进行分析.结果 bFGF在肉芽中的成纤维细胞、单核巨噬细胞、多核巨噬细胞、间质细胞、成骨细胞和骨细胞中表达:1周时以C组表达较强,2、4周时以A、B、C组表达仍较强,A、B、C组与D、E组相比差异有统计学意义(P＜0.01).结论电穿孔介导的基因治疗能使bFGF在牵引区的表达增强和表达时限延长,发挥其生理作用,促进细胞的分裂增殖与分化及牵引区细胞基质的形成和新骨生成.这可能是基因治疗促进牵引区新骨生成的机制之一.
목적 탐토전천공개도적기인치료대토하합골견인성골과정중감성성섬유세포생장인자(basic fibroblast growth factor,bFGF)표체적영향.방법 신서란대백토쌍측하합골절골,술후3d개시이0.8 mm/d속도행하합골견인,련속견인7d,장실험동물분위:A、B、C、D、E5조.분별재견인구주사2μg중조질립pIRES-hVEGF165-hBMP2、pIRES-hBMP2、pIRES-hVEGF165、공질립pIRES급생리염수.각조실험동물균시가전천공자격.각조분별우고정기제7、14、28천처사동물취재행면역조직화학검사bFGF적표체,병이용병리도상분석계통진행분석.결과 bFGF재육아중적성섬유세포、단핵거서세포、다핵거서세포、간질세포、성골세포화골세포중표체:1주시이C조표체교강,2、4주시이A、B、C조표체잉교강,A、B、C조여D、E조상비차이유통계학의의(P＜0.01).결론 전천공개도적기인치료능사bFGF재견인구적표체증강화표체시한연장,발휘기생리작용,촉진세포적분렬증식여분화급견인구세포기질적형성화신골생성.저가능시기인치료촉진견인구신골생성적궤제지일.
Objective To investigate the effect of gene therapy which was mediated by electroporation on the expression of basic fibroblast growth factor (bFGF) duning mandible distraction.Methods Bilateral mandibular osteotomies were performed in New-Zealand rabbit.After a latency of 3 days,the mandibles were elongated using distractors with a rate of 0.8 mm/d for 7 days.The rabbits were randomly divided into 5 groups:2 μtg recombinant plasmids pIRES-hVEGF165-hBMP2,pIRES-hBMP2,pIRES-hVEGF165,pIRES and normal saline (NS) were injected into the distraction area of groups A,B,C,D and E,after completion of distraction,respectively.The lengthened mandibles were harvested and processed for immunohistochemical detection of bFGF,and the mean optic densities and integral optical density of bFGF positive cells were measured by computerized image analyzer.Results bFGF mainly located in fibroblasts,giant monocytes,polynuclear phagocytes,osetocytes,and osetoblasts in the connective tissue around bone tissue.The strongest expression was observed at the 7th day,and weakened at 14th day of consolidation stage,there were no significant difference among groups A,B and C,at the 7th day of consolidation.However,there were significant differences between gene therapy groups (A,B and C) and control groups (D and E) (P＜0.01).Conclusions Gene therapy can enhance and prolong the expression of bFGF in distraction gap,which promotes the cell differentiation and proliferation,extracellular matrix synthesis and new bone formation during distraction osteogenesis.This is probably one of the molecular mechanisms of the gene therapy promoting new bone formation in distraction gap.