STIMULATION OF FRACTURE REPAIR BY RECOMBINANT HUMAN BASIC FIBROBLAST GROWTH-FACTOR IN NORMAL AND STREPTOZOTOCIN-DIABETIC RATS

STIMULATION OF FRACTURE REPAIR BY RECOMBINANT HUMAN BASIC FIBROBLAST GROWTH-FACTOR IN NORMAL AND STREPTOZOTOCIN-DIABETIC RATS
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DOI:
10.1210/en.135.2.774
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发表时间:
1994-08-01
期刊:
影响因子:
4.8
通讯作者:
MATSUMOTO, T
MATSUMOTO, T
中科院分区:
医学2区
文献类型:
--
作者:
KAWAGUCHI, H;KUROKAWA, T;MATSUMOTO, T

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采用正常大鼠和修复能力受损的链脲佐菌素-糖尿病大鼠,观察局部应用重组人碱性成纤维细胞生长因子(rhbFGF)对骨折修复的影响。腓骨骨折后,立即将rhbFGF单次注射到骨折部位。rhbFGF的应用以剂量依赖的方式增加了正常大鼠和糖尿病大鼠的愈伤组织体积和矿物质含量,并且糖尿病大鼠的愈伤组织形成被刺激到与未治疗的正常大鼠相似的水平。rhbFGF对骨折修复的显著作用与正常和糖尿病大鼠愈合腓骨力学性能的改善有关。免疫组化染色显示,骨折后1周和3周,正常大鼠体内广泛存在内源性bFGF,尤其是在软骨痂和骨膜中,而糖尿病大鼠体内bFGF含量较少。胰岛素治疗可恢复糖尿病大鼠bFGF的免疫染色。上述结果表明,bFGF在骨折修复早期有表达,糖尿病大鼠骨折修复能力受损与骨折部位bFGF表达减少有关。骨折后立即单次应用bFGF,不仅可以促进正常大鼠的修复过程,而且可以恢复糖尿病大鼠受损的修复能力。这些结果表明,局部应用bFGF可以促进受损患者的骨愈合和正常的修复能力。
The effect of local application of recombinant human basic fibroblast growth factor (rhbFGF) on fracture repair was examined using normal rats and streptozotocin-diabetic rats with impaired repairing ability. Immediately after fracturing the fibula, rhbFGF was applied by a single injection to the fracture site. Application of rhbFGF increased the volume and mineral content of callus in a dose-dependent manner in both normal and diabetic rats, and callus formation of diabetic rats was stimulated to levels similar to those in nontreated normal rats. The marked effect of rhbFGF on fracture repair was associated with an improvement in the mechanical properties of the healing fibula in both normal and diabetic rats. Immunohistochemical staining showed that endogenous bFGF was widely distributed in normal rats 1 and 3 weeks after fracture, especially in the soft callus and periosteum, whereas much less bFGF was detected in diabetic rats. Insulin treatment of diabetic rats restored the immunostaining for bFGF. These results demonstrate that bFGF is expressed during the early stage of fracture repair, and that the impaired fracture-repairing ability in diabetic rats is associated with reduced expression of bFGF at the fracture site. A single application of bFGF immediately after fracture not only facilitates the repair process in normal rats, but also recovers the impaired repairing ability in diabetic rats. These results suggest that local application of bFGF may facilitate bone union in patients with impaired as well as normal repairing ability.