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组织型纤溶酶原激活剂对微循环水平白细胞与内皮细胞相互作用的影响。

Effect of tissue-plasminogen activator on leukocyte-endothelial interactions at the microcirculatory level.

作者信息

Krapohl B D, Siemionow M, Zins J E

机构信息

Department of Plastic and Reconstructive Surgery, the Cleveland Clinic Foundation, Ohio, USA.

出版信息

Plast Reconstr Surg. 1998 Dec;102(7):2388-94. doi: 10.1097/00006534-199812000-00018.

DOI:10.1097/00006534-199812000-00018
PMID:9858174
Abstract

In free tissue transfer and replantation surgery, there is a debate over whether any pharmacologic agents should be used to improve vessel patency and tissue survival. Because tissue-plasminogen activator (t-PA) is a highly effective and safe fibrinolytic, it may be useful in obtaining and maintaining vessel patency. The direct effects of t-PA on skeletal muscle hemodynamics and leukocyte activation at the microcirculatory level were investigated. Male Sprague-Dawley rats (n = 20) were divided into three experimental groups: control (n = 8), vehicle (n = 6), and t-PA (n = 6). Using the cremaster muscle flap model and intravital microscopy, red blood cell velocity, vessel diameter, capillary perfusion, endothelial edema index, and leukocyte-endothelial interactions (rolling, adhering, and transmigrating leukocytes) in postcapillary venules were measured. In the vehicle and t-PA groups, vehicle or t-PA was infused by means of a catheter inserted into the lower abdominal aorta for local infusion. Except for a significant reduction in the diameter of the first order arterioles from 117 microm to 82 microm (medians; p = 0.026), t-PA did not significantly affect red blood cell velocity, vessel diameter, or capillary perfusion compared with vehicle. However, leukocyte-endothelial interactions did differ significantly in postcapillary venules. Adhering leukocytes counted per visual field decreased from 4.67 in the vehicle group and 3.50 in the control group to 1.67 in the t-PA group (medians; p = 0.015 and p = 0.005, respectively); transmigrating leukocytes in the t-PA group decreased from 4.75 in the vehicle group and 3.50 in the control group to 1.67 in the t-PA group (medians; p = 0.002 and p = 0.043, respectively). t-PA treatment significantly decreased the number of both adhering and transmigrating leukocytes. These novel findings on leukocyte-endothelial interactions suggest that t-PA has anti-inflammatory effect.

摘要

在游离组织移植和再植手术中,对于是否应使用任何药物来改善血管通畅性和组织存活率存在争议。由于组织型纤溶酶原激活剂(t-PA)是一种高效且安全的纤维蛋白溶解剂,它可能有助于实现并维持血管通畅。本研究调查了t-PA对骨骼肌血流动力学以及微循环水平白细胞激活的直接影响。将雄性Sprague-Dawley大鼠(n = 20)分为三个实验组:对照组(n = 8)、赋形剂组(n = 6)和t-PA组(n = 6)。使用提睾肌皮瓣模型和活体显微镜,测量了毛细血管后微静脉中的红细胞速度、血管直径、毛细血管灌注、内皮水肿指数以及白细胞与内皮细胞的相互作用(滚动、黏附及迁移的白细胞)。在赋形剂组和t-PA组中,通过插入腹主动脉下部的导管注入赋形剂或t-PA进行局部灌注。与赋形剂相比,除了一级小动脉直径从117微米显著减小至82微米(中位数;p = 0.026)外,t-PA对红细胞速度、血管直径或毛细血管灌注没有显著影响。然而,毛细血管后微静脉中的白细胞与内皮细胞相互作用确实存在显著差异。每个视野中黏附的白细胞数量从赋形剂组的4.67和对照组的3.50降至t-PA组的1.67(中位数;分别为p = 0.015和p = 0.005);t-PA组中迁移的白细胞数量从赋形剂组的4.75和对照组的3.50降至t-PA组的1.67(中位数;分别为p = 0.002和p = 0.043)。t-PA治疗显著减少了黏附和迁移的白细胞数量。这些关于白细胞与内皮细胞相互作用的新发现表明t-PA具有抗炎作用。

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