Waltham Matthew, Burnand Kevin G, Collins Michael, McGuinness Catharine L, Singh Inderjit, Smith Alberto
Academic Department of Surgery, Guys', King's, and St Thomas' Medical School, St. Thomas' Campus, London, UK.
Thromb Haemost. 2003 Jan;89(1):169-76.
Vascular endothelial growth factor (VEGF) is a regulator of physiological and pathological angiogenesis and is found in naturally resolving experimental venous thrombi, where it may also regulate recanalisation. In this study VEGF protein was injected into venous thrombi to determine if this enhanced recanalisation and organisation. A rat model of inferior vena cava (IVC) thrombosis was used. Thrombi were formed in 3 groups (n = 3 per group). 10 micro l (125)I-VEGF was directly injected into thrombus thirty minutes after induction. Three hours, 1 day and 6 days later thrombus, IVC, and other tissues were harvested. (125)I-VEGF was mostly distributed in the thrombus and the IVC, with smaller amounts in other tissues. Thrombi were formed in a further 4 groups (n = 6 per group). Thirty minutes after induction control solution or 1 ng, 10 ng or 100 ng recombinant human VEGF(165) was injected directly into the thrombus. Lumen recanalisation, thrombus organisation and monocyte content were measured on digitised sections by image analysis. In animals treated with 10 ng of VEGF there was a greater area of lumen recanalisation [mean 5492 pixels, standard error of mean (sem) 922] compared to controls (mean 2974, sem 385) (P = 0.005). There was a significant increase in the organisation score in all treated animals (1 ng: mean 70, sem 1.7, P = 0.0025; 10 ng: mean 70, sem 2.0, P = 0.0042; 100 ng: mean 72, sem 1.9, P = 0.0003) compared to controls (mean 63, sem 1.7). The monocyte content was lower in the animals treated with 1 ng VEGF (mean 3.8% of thrombus area, sem 0.3%) compared to controls (mean 5.5%, sem 0.4%) (P = 0.0008). The proportion of monocytes migrating to the centre of the thrombus increased in a dose-related manner. VEGF may prove to be of use in the treatment of venous thrombosis.
血管内皮生长因子（VEGF）是生理和病理血管生成的调节因子，在自然溶解的实验性静脉血栓中也有发现，它可能还参与调节再通。在本研究中，将VEGF蛋白注入静脉血栓中，以确定其是否能增强再通和机化。使用大鼠下腔静脉（IVC）血栓形成模型。将大鼠分为3组（每组n = 3）形成血栓。诱导血栓形成30分钟后，将10 μl（125）I-VEGF直接注入血栓内。3小时、1天和6天后，采集血栓、IVC及其他组织。（125）I-VEGF主要分布在血栓和IVC中，在其他组织中的量较少。另外将大鼠分为4组（每组n = 6）形成血栓。诱导血栓形成30分钟后，将对照溶液或1 ng、10 ng或100 ng重组人VEGF（165）直接注入血栓内。通过图像分析在数字化切片上测量管腔再通、血栓机化和单核细胞含量。与对照组（平均2974像素，标准误385）相比，接受10 ng VEGF治疗的动物管腔再通面积更大（平均5492像素，标准误922）（P = 0.005）。与对照组（平均63，标准误1.7）相比，所有接受治疗的动物机化评分均显著增加（1 ng：平均70，标准误1.7，P = 0.0025；10 ng：平均70，标准误2.0，P = 0.0042；100 ng：平均72，标准误1.9，P = 0.0003）。与对照组（平均5.5%，标准误0.4%）相比，接受1 ng VEGF治疗的动物单核细胞含量较低（平均占血栓面积的3.8%，标准误0.3%）（P = 0.0008）。迁移至血栓中心的单核细胞比例呈剂量依赖性增加。VEGF可能在静脉血栓治疗中具有应用价值。
