Bazargani Farhan, Albrektsson Ann, Yahyapour Noushin, Braide Magnus
Department of Anatomy and Cell Biology, University of Göteborg, Göteborg, Sweden.
Perit Dial Int. 2005 Jul-Aug;25(4):394-404.
Clinical studies have demonstrated that the intraperitoneal (IP) complement and coagulation systems are activated in peritoneal dialysis (PD) patients. In animal models, low molecular weight heparin (LMWH) was seen to inhibit peritoneal angiogenesis, and related compounds have increased ultrafiltration volumes after repeated administration to PD patients. The present study evaluated the effects of LMWH on ultrafiltration, coagulation, and complement activation during a single PD dwell.
Rats were exposed to a single dose of 20 mL 2.5% glucose-based, filter-sterilized PD fluid, with or without supplementation with LMWH. The PD fluid was administered either as an IP injection or as an infusion through an indwelling catheter. The dwell fluid was analyzed 2 hours later concerning activation of the complement and coagulation cascades, chemotactic activity, neutrophil recruitment, ultrafiltration volume, and glucose and urea concentrations.
Exposure to PD fluid induced activation of IP complement [formation of C3a (desArg) and increase of C5a-dependent chemotactic activity] and coagulation (formation of thrombin-antithrombin complex) and recruitment of neutrophils. In the case of IP injection, neutrophil recruitment and complement activation were inhibited by LMWH. In both models, LMWH inhibited thrombin formation, reduced complement-dependent chemotactic activity, and increased the IP fluid volume, indicating an improved ultrafiltration.
The acute inflammatory reaction to PD fluid involves the complement and coagulation cascades. Addition of LMWH to the PD fluid improves ultrafiltration, inhibits formation of thrombin, and potentially blocks C5a activity. The present results motivate further investigations of the IP cascade systems in PD.
临床研究表明，腹膜透析（PD）患者的腹膜内（IP）补体和凝血系统被激活。在动物模型中，低分子量肝素（LMWH）可抑制腹膜血管生成，相关化合物在反复给予PD患者后可增加超滤量。本研究评估了LMWH在单次PD留腹期间对超滤、凝血和补体激活的影响。
将大鼠暴露于单剂量20 mL基于2.5%葡萄糖的、经滤器灭菌的PD液，添加或不添加LMWH。PD液通过IP注射或经留置导管输注给药。2小时后分析留腹液的补体和凝血级联激活、趋化活性、中性粒细胞募集、超滤量以及葡萄糖和尿素浓度。
暴露于PD液可诱导IP补体激活[C3a（去精氨酸）形成及C5a依赖性趋化活性增加]、凝血（凝血酶 - 抗凝血酶复合物形成）以及中性粒细胞募集。在IP注射的情况下，LMWH可抑制中性粒细胞募集和补体激活。在两种模型中，LMWH均抑制凝血酶形成，降低补体依赖性趋化活性，并增加IP液量，表明超滤得到改善。
对PD液的急性炎症反应涉及补体和凝血级联反应。在PD液中添加LMWH可改善超滤，抑制凝血酶形成，并可能阻断C5a活性。本研究结果促使对PD中的IP级联系统进行进一步研究。
