Roesken F, Vollmar B, Rücker M, Seiffge D, Menger M D
Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
J Vasc Surg. 1998 Sep;28(3):498-505. doi: 10.1016/s0741-5214(98)70136-3.
This study was undertaken to evaluate in vivo the effect of recombinant hirudin (r-hirudin [HBW 023]), a potent thrombin inhibitor, on the process of microvascular thrombus formation and recanalization.
Thrombosis was induced photochemically in distinct arterioles (n = 25) and venules (n = 30) of the ear of 16 hairless hr/hr mice (8 to 10 weeks old, 25 to 30 g of body weight). r-Hirudin (1 mg/kg of body weight) was administered intravenously directly before thrombus induction; saline-treated animals served as controls. Thrombus formation (i.e., first platelet deposition at the endothelial lining [FPD]; inner luminal diameter reduction to 50% [D/2]; complete vessel occlusion [CVO]), vessel recanalization, microcirculatory parameters, and leukocyte-endothelial cell interaction were analyzed by means of intravital fluorescence microscopy.
Hirudin significantly delayed the process of thrombus formation compared with saline-treated controls in both arterioles (FPD: 381 +/- 80 vs 137 +/- 25 seconds, P < 0.05; D/2: 627 +/- 49 vs 501 +/- 71 seconds; CVO: 925 +/- 78 vs 854 +/- 60 seconds) and venules (FPD: 173 +/- 11 vs 59 +/- 4 seconds; D/2: 342 +/- 54 vs 228 +/- 27 seconds; CVO: 541 +/- 85 vs 344 +/- 43 seconds; P < 0.05). In addition, r-hirudin-treated animals showed an increased rate of vessel recanalization at 24 hours after thrombus induction (arterioles: 54% [7 of 13] vs 0% [0 of 12], P < 0.05; venules: 77% [10 of 13] vs 53% [9 of 17]), whereas microcirculatory parameters and leukocyte-endothelial cell interaction were not affected.
Our data indicate that r-hirudin not only counteracts the process of thrombus formation but also promotes vessel recanalization, thus supporting its use in clinical microvascular surgery.
本研究旨在体内评估重组水蛭素（r - 水蛭素[HBW 023]），一种强效凝血酶抑制剂，对微血管血栓形成和再通过程的影响。
在16只无毛hr/hr小鼠（8至10周龄，体重25至30克）耳部的不同小动脉（n = 25）和小静脉（n = 30）中通过光化学诱导血栓形成。在血栓诱导前直接静脉注射r - 水蛭素（1毫克/千克体重）；用生理盐水处理的动物作为对照。通过活体荧光显微镜分析血栓形成（即内皮衬里首次血小板沉积[FPD]；管腔内直径减小至50%[D/2]；血管完全闭塞[CVO]）、血管再通、微循环参数以及白细胞与内皮细胞的相互作用。
与用生理盐水处理的对照相比，水蛭素在小动脉（FPD：381±80秒对137±25秒，P < 0.05；D/2：627±49秒对501±71秒；CVO：925±78秒对854±60秒）和小静脉（FPD：173±11秒对59±4秒；D/2：342±54秒对228±27秒；CVO：541±85秒对344±43秒；P < 0.05）中均显著延迟了血栓形成过程。此外，r - 水蛭素处理的动物在血栓诱导后24小时显示出血管再通率增加（小动脉：54%[13只中的7只]对0%[12只中的0只]，P < 0.05；小静脉：77%[13只中的10只]对53%[17只中的9只]），而微循环参数和白细胞与内皮细胞的相互作用未受影响。
我们的数据表明，r - 水蛭素不仅能对抗血栓形成过程，还能促进血管再通，因此支持其在临床微血管手术中的应用。
