School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Thromb Res. 2010 Apr;125 Suppl 1(Suppl 1):S74-7. doi: 10.1016/j.thromres.2010.01.043. Epub 2010 Feb 19.
Wound healing involves a number of physiologic mechanisms including coagulation, inflammation, formation of granulation tissue, and tissue remodeling. Coagulation with robust thrombin generation leading to fibrin formation is necessary for wound healing. It is less clear if there is a requirement for ongoing coagulation to support tissue remodeling. We have studied wound healing in mice with defects in both the initiation (low tissue factor) and propagation (hemophilia B) phases. In hemophilia B mice, dermal wound healing is delayed; this delay is associated with bleeding into the granulation tissue. Mice can be treated with replacement therapy (factor IX) or bypassing agents (factor VIIa) to restore thrombin generation. If treated just prior to wound placement, mice will have normal hemostasis in the first day of wound healing. As the therapeutic agents clear, the mice will revert to hemophilic state. If the primary role of coagulation in wound healing is to provide a stable platelet/fibrin plug that is loaded with thrombin, then treating hemophilic animals just prior to wound placement should restore normal wound healing. The results from this study did not support that hypothesis. Instead the results show that restoring thrombin generation only at the time of wound placement did not improve the delayed wound healing. In preliminary studies on low tissue factor mice, there also appears to be a delay in wound healing with evidence of bleeding into the granulation tissue. The current data suggests that ongoing coagulation function needs to be maintained to support a normal wound healing process.
伤口愈合涉及多种生理机制，包括凝血、炎症、肉芽组织形成和组织重塑。凝血过程中产生的大量凝血酶导致纤维蛋白形成，这对伤口愈合是必要的。但目前尚不清楚是否需要持续的凝血来支持组织重塑。我们研究了启动（组织因子水平低）和传播（乙型血友病）阶段都存在缺陷的小鼠的伤口愈合情况。在乙型血友病小鼠中，皮肤伤口愈合延迟；这种延迟与肉芽组织中的出血有关。可以通过替代疗法（因子 IX）或旁路制剂（因子 VIIa）来治疗这些小鼠，以恢复凝血酶生成。如果在放置伤口之前进行治疗，那么在伤口愈合的第一天，小鼠的止血功能将恢复正常。随着治疗药物的清除，小鼠将恢复血友病状态。如果凝血在伤口愈合中的主要作用是提供一个稳定的血小板/纤维蛋白塞，其中充满凝血酶，那么仅在放置伤口之前治疗血友病动物应该可以恢复正常的伤口愈合。本研究的结果并不支持这一假设。相反，结果表明，仅在放置伤口时恢复凝血酶生成并不能改善延迟的伤口愈合。在组织因子水平低的小鼠的初步研究中，也似乎存在伤口愈合延迟的情况，并有证据表明肉芽组织中有出血。目前的数据表明，需要维持持续的凝血功能以支持正常的伤口愈合过程。
