Studies in flexor tendon wound healing:: Neutralizing antibody to TGF-β1 increases postoperative range of motion
Studies in flexor tendon wound healing:: Neutralizing antibody to TGF-β1 increases postoperative range of motion
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DOI：
10.1097/00006534-200001000-00025
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发表时间：
2000-01-01
影响因子：
3.6
通讯作者：
Lineaweaver, WC
中科院分区：
文献类型：
--
作者：
Chang, J;Thunder, R;Lineaweaver, WC
手部屈肌腱修复的术后结果仍然受到肌腱粘连的限制，肌腱粘连会妨碍正常的运动范围。最近使用原位杂交技术的研究表明，转化生长因子 β-1 (TGF-β 1) 参与了内在和外在的修复机制。 TGF-β1 是一种生长因子，在伤口愈合中发挥多种作用，并且还与过度疤痕形成的发病机制有关。本研究的目的是检验TGF-β1中和抗体在兔II区屈肌腱伤口愈合模型中的作用。22只成年新西兰白兔接受了II区中指深屈肌腱的完全横断。立即修复肌腱并接受以下物质之一的术中浸润：（1）对照磷酸盐缓冲盐水； (2) 50μg TGF-β1中和抗体； (3)TGF-β1和TGF-β2的中和抗体各50μg。对8只未进行手术的兔子进行分析，以确定其近端和远端指间关节的正常屈曲运动范围，使用施加于指深屈肌腱的1.2-N轴向负载。所有接受手术的兔子都被放置在石膏中8周，以允许静脉内最大腱粘连，然后被处死以确定它们的屈曲运动范围。使用Student's 未配对t 检验进行统计分析。当对未进行手术的兔子前爪使用1.2 N 负载时，近端和远端指间关节的正常组合屈曲范围为93 +/- 0 度。先前的石膏固定并没有减少这些前爪的运动范围（93 +/- 4 度）。在实验组中，完全横断并修复指深屈肌腱并渗透对照磷酸盐缓冲盐水溶液导致近端和远端指骨之间的运动范围显着减小[15 +/- 6 度（n = 8）]。然而，在用 TGF-β 1 中和抗体浸润的肌腱修复中，屈曲运动范围增加至 32 +/- 9 度（n = 7；p = 0.002）。有趣的是，TGF-β 1 和 TGF-β 2 中和抗体的组合并没有改善术后活动范围 [18 +/- 4 度（n = 7；p = 0.234）]。这些数据表明（1）兔屈肌腱修复模型可用于根据近端和远端指骨之间的屈曲程度量化肌腱疤痕形成； (2)术中浸润TGF-β1中和抗体可改善屈肌腱偏移； (3)TGF-β2中和抗体的同时渗透消除了这种效应。由于 TGF-β1 被认为与过度疤痕形成的发病机制有关，因此本文提出的研究结果表明，术中对 TGF-β1 水平的生化调节可限制屈肌腱粘连的形成。
The postoperative outcome of hand flexor tendon repair remains limited by tendon adhesions that prevent normal range of motion. Recent studies using in situ hybridization techniques harle implicated transforming growth factor beta-1 (TGF-beta 1) in both intrinsic and extrinsic mechanisms of repair. TGF-beta 1 is a growth factor that plays multiple roles in wound healing and has also been implicated in the pathogenesis of excessive scar formation. The purpose of this study was to examine the effect of neutralizing antibody to TGF-beta 1 in a rabbit zone II flexor tendon wound-healing model.Twenty-two adult New Zealand White rabbits underwent complete transection of the middle digit flexor digitorum profundus tendon in zone II. The tendons were immediately repaired and received intraoperative infiltration of one of the following substances: (1) control phosphate-buffered saline; (2) 50 mu g neutralizing antibody to TGF-beta 1; (3) 50 mu g each of neutralizing antibody to TGF-beta 1 and to TGF-beta 2. Eight rabbit that had not been operated on underwent analysis for determination of normal flexion range of motion at their proximal and distal interphalangeal joints, using a 1.2-N axial load applied to the flexor digitorum profundus tendon. All rabbits that had been operated on were placed in casts for 8 weeks to allo iv maximal tendon adhesion and were then killed to determine their flexion range of motion. Statistical analysis was performed using the Student's unpaired t test.When a 1.2-N load was used on rabbit forepaws that had not been operated on, normal combined flexion range of motion at the proximal and distal interphalangeal joints was 93 +/- 0 degrees. Previous immobilization in casts did not reduce the range of motion in these forepaws (93 +/- 4 degrees). In the experimental groups, complete transection and repair of the flexor digitorum profundus tendon with infiltration of control phosphate-buffered saline solution resulted in significantly decreased range of motion between the proximal and distal phalanges [15 +/- 6 degrees (n = 8)]. However, in the tendon repairs infiltrated with neutralizing antibody to TGF-beta 1, flexion range of motion increased to 32 +/- 9 degrees (n = 7; p = 0.002). Interestingly, a combination of neutralizing antibody to TGF-beta 1 and that to TGF-beta 2 did not improve postoperative range of motion [18 +/- 4 degrees (n = 7; p = 0.234)].These data demonstrate that (1) the rabbit flexor tendon repair model is useful for quantifying tendon scar formation on the basis of degrees of flexion between proximal and distal phalanges; (2) intraoperative infiltration of neutralizing antibody to TGF-beta 1 improves flexor tendon excursion; and (3) simultaneous infiltration of neutralizing antibody to TGF-beta 2 nullifies this effect. Because TGF-beta 1 is thought to contribute to the pathogenesis of excessive scar formation, the findings presented here suggest that intraoperative biochemical modulation of TGF-beta 1 levels limits flexor tendon adhesion formation.