Warren W C, Mustoe T A, Glenn K C
Monsanto Company, St. Louis, MO 63167.
Pept Res. 1992 Nov-Dec;5(6):331-5.
An ordered sequence of events occurs following tissue damage to bring about healing. One molecule involved in this process is thrombin. Utilizing rat linear incision and full dermal excision models, we have investigated the ability of two thrombin-derived RGD-containing peptides, p517 and p508, to enhance tissue repair under normal and healing-impaired conditions. p508, at 0.5 micrograms peptide per wound, produced a significant .23% improvement in wound strength in a dose-dependent manner. Similarly, a single application of 0.5 micrograms p517 per 6-cm linear incision would significantly increased wound-breaking strength approximately 18% at nine days postsurgery (control: 3.95 +/- 0.13 Newtons, vs. p517: 4.68 +/- 0.13 Newtons; P < 0.001). However, in glucocorticoid-stressed rats, the application of 0.5 micrograms per wound p508 or 517 did not significantly influence steroid-impaired healing. In the full dermal skin excision wound model, a single application of 0.5 micrograms p508 per wound at the time of surgery significantly reduced average wound area at days 3 and 5, when healing was impaired by glucocorticoid administration. Wound area was also reduced by p508 treatment at day 3 in the normal animal, but this effect was not statistically significant. We suggest wound-healing benefits of p508 and p517 may activate wound fibroblast proliferation or stimulate other cell types in the wound site through an RGD-mediated interaction.
组织损伤后会发生一系列有序的事件以实现愈合。凝血酶是参与这一过程的一种分子。利用大鼠线性切口和全层皮肤切除模型，我们研究了两种源自凝血酶的含RGD肽p517和p508在正常和愈合受损条件下促进组织修复的能力。每伤口给予0.5微克肽的p508以剂量依赖的方式使伤口强度显著提高了23%。同样，每6厘米线性切口单次应用0.5微克p517在术后九天可使伤口破裂强度显著增加约18%（对照组：3.95±0.13牛顿，p517组：4.68±0.13牛顿；P<0.001）。然而，在糖皮质激素应激的大鼠中，每伤口应用0.5微克p508或517对类固醇损害的愈合没有显著影响。在全层皮肤切除伤口模型中，手术时每伤口单次应用0.5微克p508在第3天和第5天显著减小了平均伤口面积，此时糖皮质激素给药会损害愈合。在正常动物中，p508处理在第3天也减小了伤口面积，但这种效果没有统计学意义。我们认为p508和p517对伤口愈合的益处可能是通过RGD介导的相互作用激活伤口成纤维细胞增殖或刺激伤口部位的其他细胞类型。
