Activated protein C as a promoter of wound healing

伤口的愈合是一个复杂的过程，涉及多个阶段，包括凝固、炎症、重塑和最终形成完整的皮肤。外周动脉闭塞性疾病、深静脉血栓形成、糖尿病、压疮和烧伤患者会出现伤口愈合受损和/或皮肤溃疡。尽管进行了深入的研究，但与愈合受损相关的确切机制尚不清楚。APC是一种丝氨酸蛋白酶，在生理抗凝中起核心作用。APC有效激活明胶酶A，这种酶在伤口愈合和血管生成的重塑阶段起着重要作用。我们的初步实验提供了非常有力的证据，证明APC在培养细胞和大鼠皮肤损伤模型中都能加速伤口愈合。这项研究有三个目的。第一个将使用细胞培养技术来研究APC在伤口愈合过程中的作用机制。其次，我们将扩大APC作为促进伤口愈合的体内效应的试点研究。这些研究将使用大鼠伤口愈合模型来检查APC的确切剂量和时间制度。此外，我们将测试APC对糖尿病大鼠缓慢愈合伤口的影响。第三，我们将确定与正常愈合的伤口相比，来自缓慢愈合伤口的人体伤口液中APC是否在数量上或功能上缺乏。这是APC首次与伤口愈合有关。据设想，这项工作将最终导致APC的一种新的局部治疗，以加速缓慢愈合的伤口。

The healing of wounds is a complex process involving a number of stages, including coagulation, inflammation, remodelling and finally development of full strength skin. Impaired wound healing and-or skin ulcers occur in patients with peripheral arterial occlusive disease, deep vein thrombosis, diabetes, pressure sores and burns. Despite intense investigation, the precise mechanisms associated with impaired healing are poorly understood. APC is a serine protease that plays a central role in physiological anticoagulation. APC potently activates gelatinase A, an enzyme that plays a prominent role during the remodelling phase of wound healing and angiogenesis. Our preliminary experiments provide very strong evidence that APC accelerates wound healing using both cultured cells and a rat skin wounding model. There are three aims to this study. The first will use cell culture techniques to investigate the mechanisms of action of APC during wound healing. Secondly, we will expand our pilot studies on the effect of APC as a promoter of wound healing in vivo. These studies will examine the exact dosing and timing regime for APC, using a rat wound healing model. In addition, we will test the effect of APC on slow healing wounds, present in diabetic rats. Thirdly, we will determine whether APC is quantitatively or functionally deficient in human wound fluid derived from slow-healing wounds compared to wounds that heal normally. This is the first time that APC has been implicated in wound healing. It is envisaged that this work will ultimately lead to a novel topical treatment of APC to accelerate slow-healing wounds.