Lanning D A, Diegelmann R F, Yager D R, Wallace M L, Bagwell C E, Haynes J H
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
J Pediatr Surg. 2000 Feb;35(2):183-7; discussion 187-8. doi: 10.1016/s0022-3468(00)90007-1.
BACKGROUND/PURPOSE: In a noncontractile fetal rabbit model, the authors recently have shown the induction of excisional wound contraction with sustained-release cellulose implants formulated with transforming growth factor (TGF)-beta. The purpose of this study was to test the hypothesis that the excisional wound contraction in this model is associated with the induction of myofibroblasts in the surrounding dermis, demonstrated by the presence of alpha-smooth muscle actin.
Cellulose discs were formulated with either 1.0 microg of TGF-beta1 (n = 6); 1.0 microg of TGF-beta3 (n = 9); 10 microg of TGF-beta3 (n = 6); or their carrier protein, bovine serum albumin (BSA; n = 9), for sustained-release over 5 days. Each disc was implanted into a subcutaneous pocket on the back of a fetal New Zealand White rabbit in utero on day 24 of gestation (term, 31 days). A full-thickness, 3-mm excisional wound (7.4 mm2) was then made next to the implanted cellulose disc. All fetuses were harvested at 3 days. The amount of alpha-smooth muscle (SM) actin in the dermis around the implants and wounds was determined using immunohistochemical techniques.
Excisional wounds exposed to 1.0 microg of TGF-beta1 (5.6+/-2.0 mm2), 1.0 microg of TGF-beta3 (6.9+/-1.0 mm2), and 10 microg of TGF-beta3 (2.7+/-1.0 mm2) were significantly smaller when compared with the BSA control group (12.8+/-1.1 mm2; P<.05). Furthermore, there was a significant increase in staining for alpha-SM actin in the TGF-beta1 (1.8+/-0.5) and 10 microg TGF-beta3 (2.8+/-0.2) groups in comparison with the scant staining in the BSA control group (0.5+/-0.2; P<.05).
TGF-beta1 and -beta3 induce alpha-SM actin and contraction of cutaneous excisional wounds in a fetal noncontractile model. This model of inducible cutaneous excisional wound contraction may be useful in further determining the role of the myofibroblast in wound contraction and the physiology underlying this poorly understood aspect of wound healing.
背景/目的：在一个非收缩性的胎兔模型中，作者最近发现用转化生长因子（TGF）-β配制的缓释纤维素植入物可诱导切除伤口收缩。本研究的目的是检验这样一个假设，即该模型中的切除伤口收缩与周围真皮中肌成纤维细胞的诱导有关，这可通过α-平滑肌肌动蛋白的存在来证明。
将纤维素圆盘分别用1.0微克的TGF-β1（n = 6）、1.0微克的TGF-β3（n = 9）、10微克的TGF-β3（n = 6）或其载体蛋白牛血清白蛋白（BSA；n = 9）配制，以实现5天的缓释。在妊娠第24天（足月为31天），将每个圆盘植入子宫内新西兰白兔胎儿背部的皮下袋中。然后在植入的纤维素圆盘旁边制作一个全层3毫米的切除伤口（7.4平方毫米）。所有胎儿在3天时收获。使用免疫组织化学技术测定植入物和伤口周围真皮中α-平滑肌（SM）肌动蛋白的含量。
与BSA对照组（12.8±1.1平方毫米；P<0.05）相比，暴露于1.0微克TGF-β1（5.6±2.0平方毫米）、1.0微克TGF-β3（6.9±1.0平方毫米）和10微克TGF-β3（2.7±1.0平方毫米）的切除伤口明显更小。此外，与BSA对照组中稀少的染色（0.5±0.2；P<0.05）相比，TGF-β1组（1.8±0.5）和10微克TGF-β3组（2.8±0.2）中α-SM肌动蛋白的染色显著增加。
在胎儿非收缩性模型中，TGF-β1和-β3可诱导α-SM肌动蛋白和皮肤切除伤口的收缩。这种可诱导的皮肤切除伤口收缩模型可能有助于进一步确定肌成纤维细胞在伤口收缩中的作用以及伤口愈合这一了解甚少方面的生理学机制。
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