bFGF对rhBMP-2诱导犬气管损伤后软骨再生的作用

Enhancing effects of bFGF on regeneration of tracheal cartilage in a canine trachea injury model induced by rhBMP-2

目的:研究应用碱性成纤维细胞生长因子(bFGF)促进重组人骨形态发生蛋白-2(rhBMP-2)诱导犬气管环部分缺损后软骨再生的可行性.方法:切除连续5个气管环前端的部分软骨,形成1cm×3cm的气管原位软骨缺损,建立犬气管软骨缺损模型.将18只犬随机分为A,B,C组,每组6只,A组为对照组,于软骨缺损处未行任何处理,B组于气管软骨缺损部位植入rhBMP-2/聚乙烯吡咯烷酮(PVP)复合材料,C组于气管软骨缺损部位植入rhBMP-2/bFGF/PVP复合材料.于术后12wk处死各实验犬,行大体及组织学检查,组织学半定量测定新生软骨情况.结果:A组气管软骨损伤残端出现气管软骨软化现象,气管管腔狭窄明显,软骨缺损处未见新生软骨生成;B,C两组气管软骨损伤部位残端未见气管软化,管腔狭窄不明显,软骨缺损处可见新生软骨及软骨岛生成,其中C组诱导新生软骨面积较B组更大(P<0.05).结论:rhBMP-2/PVP及rhBMP-2/bFGF/PVP缓释系统均可诱导气管软骨再生,rhBMP-2/bFGF/PVP缓释系统效果优于rh-BMP-2/PVP缓释系统.bFGF可能具有促进rhBMP-2诱导犬气管损伤后软骨再生的作用.

AIM： To investigate whether basic fibroblast growth factor （bFGF） enhances regeneration of tracheal cartilage in trachea injured canine induced by the recombinant human bone morphogenetic protein-2 （rhBMP-2）. METHODS： A 1 cm × 3 cm gap was made in the anterior cervical trachea by removing 3 cm long strips of 5 sequential cartilages. In the control group （ n = 6）, the gaps were left untreated. In the rhBMP-2/PVP group （n=6 ）, slow release system rhBMP-2/PVP was implanted in each defect. In the rhBMP-2/bFGF/PVP group （n =6） , slow release system rhBMP-2/bFGF/PVP was implanted in each defect. The tracheas were harvested at 12 weeks postoperatively. The cervical tracheas were then removed and evaluated grossly and histopathologically. The areas of regenerated cartilage were calculated. RESULTS：Tracheomalacia and the stenosis of the tracheal lumen were observed in the control groups but no regenerated cartilage was detected in the control groups at 12 weeks after surgery. In contrast, no tracheomalacia and no obvious stenosis of the tracheal was observed in the rhBMP-2/PVP group and rhBMP-2/bF- GF/PVP groups. Regenerated cartilage was also observed in both groups at 12 weeks after surgery. This regenerated cartilage mainrained the integrity of the internal lumen for longer than 3 months. The areas of regenerated cartilage in rhBMP-2/bFGF/PVP group were larger than those in rhBMP-2/PVP group （ P 〈 0. 05 ）. CONCLUSION： Both slow release systems, rhBMP-2/PVP and rhBMP-2/bFGF/PVP, can induce regeneration of tracheal cartilage in a canine model, rhBMP-2/bFGF/PVP has stronger effect in inducing the regeneration of tracheal cartilage, indicating that bFGF may enhance rhBMP-2 to induce regeneration of rhBMP-2 induced injured tracheal cartilage.