抗凝血酶和因子 XIII 在内毒素血症期间白细胞非依赖性血浆外渗中的作用：大鼠体内显微镜研究

Role of antithrombin and factor XIII in leukocyte-independent plasma extravasation during endotoxemia: an intravital-microscopic study in the rat.

作者信息

Czabanka Marcus, Martin Eike, Walther Andreas

机构信息

Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany.

出版信息

J Surg Res. 2006 Dec;136(2):219-26. doi: 10.1016/j.jss.2005.11.574. Epub 2006 Feb 2.

DOI:10.1016/j.jss.2005.11.574

PMID:16457847

Abstract

BACKGROUND

Platelet-endothelial interactions have been shown to be main mediators of leukocyte-independent endothelial damage. Besides altering platelet-endothelial interactions, both antithrombin and factor XIII reduce microvascular permeability in leukocyte-dependent experimental models. Thus, it was our aim to investigate the effects of antithrombin and factor XIII on microvascular permeability during leukocyte-independent endotoxemia.

MATERIAL AND METHODS

In male Wistar rats, venular wall shear rate, macromolecular efflux, and leukocyte-endothelial interaction were determined in mesenteric postcapillary venules using intravital microscopy at baseline, 60, and 120 min after the start of the experiment. Fucoidin and a continuous infusion of lipopolysaccharides were used to generate leukocyte-independent endotoxemia. The experiment was divided into two parts 1) an antithrombin study and 2) a factor XIII study.

RESULTS

No differences between groups in leukocyte rolling and venular wall shear rate could be observed in both parts of the experiment. Pretreatment with antithrombin reduced microvascular permeability significantly compared with control subjects (120 min: Fuco [untreated]: 0.14 +/- 0.03; Fuco/ETX [control]: 0.37 +/- 0.06; Fuco + ATIII/ETX: 0.15 +/- 0.02; P < 0.05). Factor XIII reduced microvascular permeability significantly after 60 min (Fuco [untreated]: 0.10 +/- 0.03; Fuco/ETX [control]: 0.36 +/- 0.07; Fuco + FXIII/ETX: 0.13 +/- 0.04; P < 0.05). This effect diminished after 120 min (Fuco [untreated]: 0.12 +/- 0.03; Fuco/ETX [control]: 0.5 +/- 0.08; Fuco + FXIII/ETX: 0.29 +/- 0.05; P < 0.05).

CONCLUSIONS

Antithrombin and factor XIII reduce leukocyte-independent microvascular permeability. Yet, factor XIII also shows a nonprotective effect on a long-term basis. These data emphasize the central role of platelets in leukocyte-independent endotoxemia.

摘要

背景

血小板与内皮细胞的相互作用已被证明是白细胞非依赖性内皮损伤的主要介质。除了改变血小板与内皮细胞的相互作用外，抗凝血酶和因子 XIII 在白细胞依赖性实验模型中均可降低微血管通透性。因此，我们旨在研究抗凝血酶和因子 XIII 在白细胞非依赖性内毒素血症期间对微血管通透性的影响。

材料与方法

在雄性 Wistar 大鼠中，于实验开始时、60 分钟和 120 分钟，使用活体显微镜在肠系膜后微静脉中测定静脉壁剪切速率、大分子流出以及白细胞与内皮细胞的相互作用。采用岩藻依聚糖和持续输注脂多糖来诱导白细胞非依赖性内毒素血症。实验分为两部分：1）抗凝血酶研究；2）因子 XIII 研究。

结果

在实验的两个部分中，各实验组在白细胞滚动和静脉壁剪切速率方面均未观察到差异。与对照组相比，抗凝血酶预处理显著降低了微血管通透性（120 分钟时：岩藻依聚糖[未处理]：0.14±0.03；岩藻依聚糖/内毒素[对照]：0.37±0.06；岩藻依聚糖+抗凝血酶 III/内毒素：0.15±0.02；P<0.05）。60 分钟后，因子 XIII 显著降低了微血管通透性（岩藻依聚糖[未处理]：0.10±0.03；岩藻依聚糖/内毒素[对照]：0.36±0.07；岩藻依聚糖+因子 XIII/内毒素：0.13±0.04；P<0.05）。120 分钟后这种作用减弱（岩藻依聚糖[未处理]：0.12±0.03；岩藻依聚糖/内毒素[对照]：0.5±0.08；岩藻依聚糖+因子 XIII/内毒素：0.29±0.05；P<0.05）。