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体内肌腱愈合:早期肌腱愈合期的基因表达及多种生长因子的产生

Tendon healing in vivo: gene expression and production of multiple growth factors in early tendon healing period.

作者信息

Chen Chuan Hao, Cao Yi, Wu Ya Fang, Bais Anthony J, Gao Jing Song, Tang Jin Bo

机构信息

Department of Hand Surgery, Hand Surgery Research Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.

出版信息

J Hand Surg Am. 2008 Dec;33(10):1834-42. doi: 10.1016/j.jhsa.2008.07.003.

DOI:10.1016/j.jhsa.2008.07.003
PMID:19084187
Abstract

PURPOSE

The actions of growth factors during healing of injured flexor tendons are not well characterized, although information pertinent to some individual growth factors is available. We studied gene expression and protein production of a number of growth factors at several time points during the early healing period in a chicken model.

METHODS

Seventy-four long toes of 37 white Leghorn chickens were used. The flexor digitorum profundus tendons of 60 toes were surgically repaired after complete transection and were harvested for analysis 3, 5, 7, 9, 14, and 21 days after surgery. The expression of 6 growth factors was studied at 4 time points after surgery with real-time quantitative polymerase chain reactions, and production and distribution of 3 growth factors at all 6 time points were studied by immunohistochemical staining with antibodies. Fourteen tendons that had no surgery served as day 0 controls. Tendon healing status was also assessed histologically.

RESULTS

Throughout the early tendon healing period, connective tissue growth factor (CTGF) and transforming growth factor beta (TGF-beta) showed high levels of gene expression. Levels of gene expression of vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) were high or moderately high. Expression of the TGF-beta gene was upregulated after injury, whereas the basic fibroblast growth factor (bFGF) gene was downregulated at all postsurgical time points and expressed at the lowest levels among 6 growth factor genes 2 to 3 weeks after surgery. The platelet-derived growth factor B (PDGF-B) gene was also minimally expressed. Findings of immunohistochemistry corresponded to TGF-beta, bFGF, and IGF-1 gene expression.

CONCLUSIONS

In this model, up to 3 weeks after surgery, gene expression and production of TGF-beta are high and are upregulated in this healing period. However, expression of the bFGF gene and protein is low and decreases in the healing tendon. The CTGF, VEGF, and IGF-1 genes are expressed at high or moderately high levels, but PDGF-B is minimally expressed.

摘要

目的

尽管已有一些关于个别生长因子的相关信息,但在受伤屈肌腱愈合过程中生长因子的作用尚未得到充分描述。我们在鸡模型的早期愈合阶段的多个时间点研究了多种生长因子的基因表达和蛋白质产生情况。

方法

使用37只白来航鸡的74个长趾。对60个趾的趾深屈肌腱进行完全横断后手术修复,并在术后3、5、7、9、14和21天采集样本进行分析。通过实时定量聚合酶链反应在术后4个时间点研究6种生长因子的表达,并通过抗体免疫组织化学染色在所有6个时间点研究3种生长因子的产生和分布。14条未手术的肌腱作为第0天的对照。还通过组织学评估肌腱愈合状态。

结果

在肌腱愈合早期,结缔组织生长因子(CTGF)和转化生长因子β(TGF-β)显示出高水平的基因表达。血管内皮生长因子(VEGF)和胰岛素样生长因子1(IGF-1)的基因表达水平高或中等。TGF-β基因的表达在损伤后上调,而碱性成纤维细胞生长因子(bFGF)基因在所有术后时间点均下调,并在术后2至3周在6种生长因子基因中表达水平最低。血小板衍生生长因子B(PDGF-B)基因也表达极少。免疫组织化学结果与TGF-β、bFGF和IGF-1基因表达一致。

结论

在该模型中,术后长达3周,TGF-β的基因表达和产生量高,且在此愈合期上调。然而,bFGF基因和蛋白的表达低,且在愈合的肌腱中减少。CTGF、VEGF和IGF-1基因以高或中等水平表达,但PDGF-B表达极少。

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