Smith P D
Department of Surgery, Royal Free and University College Medical School, The Middlesex Hospital, London, UK.
Angiology. 2001 Aug;52 Suppl 1:S35-42. doi: 10.1177/0003319701052001s05.
The causes of venous ulceration remain unclear. Twentieth-century hypotheses concentrated on the possibility that this problem was caused by failure of oxygen delivery to the skin. However, it has been difficult to substantiate these predictions in practice. Although the presence of tissue hypoxia has been suggested by studies in which transcutaneous oxygen tension has been assessed with transducers heated to unphysiological temperatures, when oxygen measurements are made at room temperature there is little evidence of tissue hypoxia. This has led to the assessment of alternative mechanisms of ulcer development. There has been considerable interest in recent years in the inflammatory processes that surround venous ulceration. A complex sequence of events appears to surround the development of leg ulceration. Increased leukocyte activation has been shown in patients with venous disease as well as increased expression of soluble endothelial adhesion molecules. Histologic studies of the skin in patients with chronic venous disease show a perivascular infiltration of the capillaries of the papillary plexus (the most superficial part of the dermis) with monocytes, macrophages, and connective tissue proteins including fibrin. Fibrosis of the skin and subcutaneous tissues may be initiated by increased gene expression and production of transforming growth factor-beta1. Vascular endothelial growth factor may be involved in the capillary proliferation that has been reported in the skin by a number of authors. Increased expression of several tissue metalloproteinases has been reported both in liposclerotic skin and periulcer skin. The tissue inhibitors of metalloproteinases are also increased and the net result is unclear. Treatment of venous disease using micronized purified flavonoid fraction moderates some of the inflammatory markers, including leukocyte ligand expression and endothelial adhesion molecule shedding. These compounds have also been shown to reduce leukocyte-endothelial adhesion in animal models of ischemia-reperfusion injury. Many inflammatory processes have now been shown to be involved in the development of the skin changes in patients with chronic venous disease. However, the precise sequence of events that leads to leg ulceration is still unclear. Pharmacologic treatments aimed at moderating some of these inflammatory processes are now under investigation as potential ways of treating patients with the more advanced stages of venous disease.
静脉溃疡的病因尚不清楚。20世纪的假说集中在这样一种可能性，即这个问题是由皮肤氧气输送不足引起的。然而，在实践中很难证实这些预测。尽管通过使用加热到非生理温度的换能器评估经皮氧张力的研究表明存在组织缺氧，但在室温下进行氧测量时，几乎没有组织缺氧的证据。这导致了对溃疡形成的替代机制的评估。近年来，人们对围绕静脉溃疡的炎症过程产生了浓厚兴趣。腿部溃疡的发生似乎伴随着一系列复杂的事件。静脉疾病患者中已显示白细胞活化增加以及可溶性内皮粘附分子表达增加。对慢性静脉疾病患者皮肤的组织学研究表明，乳头层（真皮最表层）的毛细血管周围有单核细胞、巨噬细胞和包括纤维蛋白在内的结缔组织蛋白浸润。皮肤和皮下组织的纤维化可能由转化生长因子-β1的基因表达增加和产生引发。血管内皮生长因子可能参与了许多作者报道的皮肤毛细血管增殖。在脂肪硬化皮肤和溃疡周围皮肤中均报道了几种组织金属蛋白酶的表达增加。金属蛋白酶组织抑制剂也增加，但其最终结果尚不清楚。使用微粉化纯化黄酮类成分治疗静脉疾病可减轻一些炎症标志物，包括白细胞配体表达和内皮粘附分子脱落。这些化合物在缺血再灌注损伤动物模型中也已显示可减少白细胞与内皮的粘附。现已表明许多炎症过程参与了慢性静脉疾病患者皮肤变化的发展。然而，导致腿部溃疡的确切事件顺序仍不清楚。旨在减轻其中一些炎症过程的药物治疗目前正在研究中，作为治疗静脉疾病更晚期患者的潜在方法。
