Bergan J J, Schmid-Schönbein G W, Takase S
Department of Surgery, University of California, San Diego, USA.
Angiology. 2001 Aug;52 Suppl 1:S43-7. doi: 10.1177/0003319701052001S06.
Early manifestations of chronic venous insufficiency (CVI) are edema, hyperpigmentation, and lipodermatosclerosis. Late complications are cutaneous ulceration and delayed healing. The specific hallmarks of this inflammation include CD68-positive infiltration into the dermal tissue, monocytes, and lymphocytes and enhanced endothelial permeability. This may lead to "fibrin cuff" formation. In addition, membrane adhesion molecules are present and cytokine expression is seen. In one experimental model of mesenteric venous hypertension, the inflammatory process was detected in its earliest stages. This was evident in the form of neutrophilic leukocyte adhesion to venular endothelium as well as migration of cells across the endothelium and basement membrane into the interstitial space. Simultaneously, parenchymal cell death was detected. This suggests that the mechanism that triggers the inflammatory reaction is venous hypertension. This may cause venous distension and a shift in fluid shear stress. Our observations suggest that patients with venous insufficiency demonstrate circulatory humoral stimulators for leukocyte activation. Otherwise, there is evidence that the inflammatory reaction is limited to the region of the venous ulceration or at least to the skin areas with severe microangiopathy. It may be that activated leukocytes traverse perivascular cuffs and release active transforming growth factor-beta1 (TGF-beta1) which has been found to be elevated exclusively in areas of clinically active CVI. Surgical intervention markedly decreases the number of dysfunctional vein segments and allows pharmacologic agents to protect normal structures from continuing damage. Daflon 500 mg, the purified micronized flavonoid fraction containing 90% diosmin and 10% hesperidin, acts favorably in venous ulcer treatment by inhibiting the synthesis of prostaglandins and free radicals. It decreases bradykinin-induced microvascular leakage and may act favorably to inhibit leukocyte activation, trapping, and migration. Clinically, edema is reduced, ulcer healing is accelerated, and leukocyte trapping diminished. The action of micronized purified flavonoid fraction is beginning to be better understood, and as further knowledge is gained, better pharmacologic control of CVI is a tantalizing promise.
慢性静脉功能不全（CVI）的早期表现为水肿、色素沉着和脂肪皮肤硬化。晚期并发症为皮肤溃疡和愈合延迟。这种炎症的具体特征包括真皮组织中CD68阳性浸润、单核细胞和淋巴细胞以及内皮通透性增强。这可能导致“纤维蛋白袖套”形成。此外，存在膜粘附分子并可见细胞因子表达。在一个肠系膜静脉高压的实验模型中，炎症过程在其最早阶段就被检测到。这表现为嗜中性白细胞粘附于小静脉内皮以及细胞穿过内皮和基底膜迁移到间质空间。同时，检测到实质细胞死亡。这表明引发炎症反应的机制是静脉高压。这可能导致静脉扩张和流体剪切应力的改变。我们的观察表明，静脉功能不全患者表现出循环体液刺激物以激活白细胞。否则，有证据表明炎症反应局限于静脉溃疡区域或至少局限于微血管病变严重的皮肤区域。可能是活化的白细胞穿过血管周围袖套并释放活性转化生长因子-β1（TGF-β1），已发现其仅在临床活跃的CVI区域升高。手术干预显著减少功能失调静脉段的数量，并使药物能够保护正常结构免受持续损伤。Daflon 500毫克，即含有90%地奥司明和10%橙皮苷的纯化微粉化类黄酮组分，通过抑制前列腺素和自由基的合成，在静脉溃疡治疗中发挥有益作用。它减少缓激肽诱导的微血管渗漏，并可能在抑制白细胞活化、捕获和迁移方面发挥有益作用。临床上，水肿减轻，溃疡愈合加速，白细胞捕获减少。微粉化纯化类黄酮组分的作用开始得到更好的理解，随着进一步的认识，对CVI进行更好的药物控制是一个诱人的前景。
