Arnould T, Janssens D, Michiels C, Remacle J
Laboratoire de Biochimie Cellulaire, Facultés Universitaires Notre dame de la Paix, Namur, Belgium.
Eur J Pharmacol. 1996 Nov 14;315(2):227-33. doi: 10.1016/s0014-2999(96)00645-0.
Phlebotonic drugs are very often old drugs which improve symptoms in chronic venous insufficiency but their precise mechanism remains unclear. One reason for this lack of information is our poor understanding of the aetiology of the varicose vein. One hypothesis which is being more and more substantiated is that the origin of the disease lies in the activation of the endothelium during blood stasis, leading to a cascade of reactions which, in the long term, alter the structure of the vein wall. In this work, we tested aescine (Reparil i.v. form), a phlebotonic drug, in an in vitro model which mimics this situation, i.e. human endothelial cells exposed to hypoxic conditions. Aescine was shown to inhibit 2 important steps of the activation of endothelial cells incubated 120 min under hypoxia the decrease in ATP content, which is the starting point of the activation cascade, and the increase in the activity of phospholipase A2, an enzyme responsible for the release of precursors of inflammatory mediators. Hypoxia-activated endothelial cells also increase their adhesiveness for neutrophils. This process could also be prevented in a dose-dependent manner if endothelial cells were incubated in the presence of aescine. This inhibition was confirmed by morphological observations in scanning electron microscopy. All 3 effects were already evidenced at 100 ng/ml and were maximal at 750 ng/ml. These effects obtained at very low concentrations probably represent one of the main molecular and cellular mechanisms that underlie, among others, protection of the vessel wall. Objective criteria for our understanding of the preventive action of this phlebotonic drug are, thus, provided.
促静脉回流药物通常是一些老药，可改善慢性静脉功能不全的症状，但其确切机制尚不清楚。缺乏相关信息的一个原因是我们对静脉曲张病因的了解不足。越来越多证据支持的一种假说是，该病的起源在于血液淤滞期间内皮细胞的激活，导致一系列反应，长期来看会改变静脉壁的结构。在这项研究中，我们在一个模拟这种情况的体外模型中测试了促静脉回流药物七叶皂苷（静脉注射用利百素），即让人类内皮细胞暴露于缺氧条件下。结果显示，七叶皂苷可抑制缺氧条件下培养120分钟的内皮细胞激活的两个重要步骤：ATP含量的降低，这是激活级联反应的起点；以及磷脂酶A2活性的增加，该酶负责释放炎症介质的前体。缺氧激活的内皮细胞对中性粒细胞的黏附性也会增加。如果在内皮细胞培养时加入七叶皂苷，这一过程也能以剂量依赖的方式被阻止。扫描电子显微镜下的形态学观察证实了这种抑制作用。所有这三种效应在100 ng/ml时就已显现，在750 ng/ml时达到最大。在极低浓度下获得的这些效应可能代表了血管壁保护等作用背后的主要分子和细胞机制之一。因此，为我们理解这种促静脉回流药物的预防作用提供了客观标准。
