血管内皮生长因子在骨折愈合中的自分泌作用

Autocrine function of VEGF in rat fracture healing process

目的探讨血管内皮生长因子(VEGF)在骨折愈合中的自分泌作用。方法利用鼠股骨闭合性骨折模型,应用组织学和逆转录聚合酶链反应(RT-PCR)方法,观察骨折不同的愈合修复阶段中骨痂的组织学变化,检测各种相应骨痂组织中VEGF及其受体VEGFR1(Flt-1)和VEGFR2(KDR/Flk-1)的mRNA的表达。结果骨折愈合是一个高度有序的组织学变化过程,骨痂内的膜内化骨,软骨形成,软骨内化骨等过程可同时或连续出现。VEGF(251 bp)及受体Flt-1(272 bp)和KDR/Flk-1(252 bp)在骨折后第7、14天的软骨性骨痂(软骨组织)和骨性骨痂(小梁骨-膜内化骨和软骨内化骨)中均同时清晰表达。表达信号均匀,强度较大。结论骨折愈合过程中的软骨性骨痂和骨性骨痂中的软骨-骨细胞系统共表达VEGF及其两种受体,提示VEGF自分泌作用参与骨折愈合过程。

Objective To discuss the autocrine role of VEGF system in fracture healing process. Methods Closed femoral fracture models in Sprague-Dawley rats were produced and callus specimens were stained to observe the histological changes. The mRNA expression of VEGF and its receptors VEG-FR1 （Fit-1） and VEGFR2 （KDR/Flk-1） from the various calluses was detected by RT-PCR during fracture healing development. Results The process of fracture healing was correlated with the ordered temporal sequence of histological changes. The cellular events of intramembranous ossification, chodrogenesis and endochondral ossification appeared in the callussimultaneously and sequentially. The co-expression of mRNAs of VEGF （251 bp） and its receptors Flt-1 （272 bp） and KDR/Flk-1 （252 bp） was dearly detected in the chondrogenic-callus （cartilage） and the osteogenic-callus （trabecular bone-intramembranous ossification and endochondral ossification）. Conclusions The co-expression of VEGF and its receptors Flt-1 and KDR/Flk-1 was strongly detected in osteogenic and chondrogenic cells in the fracture healing process, suggesting VEGF might play an important autocrine function during fracture development.