乌司他丁对体外循环犬血浆可溶性细胞间粘附分子-1、血管性假性血友病因子及MDA水平的影响

Effects of ulinastatin on plasma levels of soluble intercellular adhesion molecule-1, von Willebrand＇s factor and MDA during cardiopulmonary bypass in dogs

目的 评价不同剂量乌司他丁对体外循环（CPB）犬血浆可溶性细胞间粘附分子-1（sICAM-1）、血管性假性血友病因子（vWF）及丙二醛（MDA）水平的影响。方法 成年健康杂种犬18只，体重10～15kg，雌雄不拘，随机分成3组（n=6）：对照组（C组）、乌司他丁Ⅰ组（U1组）和乌司他丁Ⅱ组（U2组）。U1组于CPB前经股静脉注射乌司他丁2500U／kg（溶于20ml生理盐水中），CPB预充液中给予乌司他丁2500U／kg；U2组于CPB前经股静脉注射乌司他丁5000U／kg（溶于20ml生理盐水中），CPB预充液中给予乌司他丁5000U／kg；C组在CPB前经股静脉注射生理盐水20ml。3组于CPB前即刻（T1）、升主动脉阻断后15min（T1）、45min（T3）、升主动脉开放后30min（T4）、60min（T5）取股静脉血5ml，4000r/min离心5min，分别用酶联免疫吸附双抗体夹心法测定血浆sICAM-1和vWF水平、生物化学发光法测定MDA水平，相同时点截取股动脉做光镜下病理学检查，观察血管内皮细胞的变化。结果 与T1相比，C组各时点血浆sICAM-1、vWF、MDA的水平均增高（P〈0．05或0．01），经乌司他丁处理后，虽然各指标水平也增高，但与C组相比，U1组T5时血浆MDA水平降低（P〈0．05），U2组T4，5时血浆sICAM、T2-5时血浆vWF、T3-5时血浆MDA水平降低（P〈0．05或0．01）。光镜下病理学检查发现C组各时点血管内皮细胞损害程度较U1组、U2组严重，U2组内皮完整性好于U1组。结论 乌司他丁10000U／kg可一定程度地抑制体外循环犬血浆sICAM-1、vWF、MDA的水平，对血管内皮细胞起到保护作用。

Objective To investigate the effects of ulinastatin on plasma levels of soluble intercellular adhesion molecule-1 （sICAM-1）, van Willebrand＇ s factor （vMF） and malondialdehyde （MDA） during cardiopulmonary bypass （CPB）. Methods Eighteen healthy adult mongrel dogs of both sexes weighing 10-15 kg were randomly divided into 3 groups （ n = 6 each） ： Ⅰ control group; Ⅱ ulinastatin group 1 （U,） and Ⅲ ulinastatin group 2 （ U2 ）. The animals were anesthetized with intraperitoneal 2.5 % pentobarbital 25 mg· kg^-1 , intubated and mechanically ventilated. Femoral artery and vein Were cannulated for MAP and CVP monitoring and blood sampling. CPB was performed using Sarns 5000 heart-lung machine （3M Co. USA） with bubble oxygenator. The priming volume was 500 ml of HES and 500 ml of balanced NaCl solution. Group U1 and U2 received ulinastatin 5 000 and 10 000 U·kg^-1 （ half was injected Ⅳ and the other half added to the prime） respectively. The control group received normal saline instead of ulinastatin. Blood samples and femoral artery tissues were obtained before CPB （T1, baseline）, 15 and 45 rain after aortic cross-clamping （T2, T3 ） and 30 and 60 min after release of aortic cross-clamp （T4 ,T5 ） for determination of plasma levels of sICAM-1, vWF, MDA and microscopic examination. Results The plasma levels of slCAM-1, vWF and MDA were significantly increased during CPB as compared with the baseline values at T1 . The increase in plasma slCAM-1, vWF and MDA levels induced by CPB was significantly attenuated in group U1 and U2. The vascular endothelium was seriously damaged or exfoliated during CPB especially at T5 and ulinastatin significantly ameliorated the CPB-induced damage in a dose-dependent manner. Conclusions The endothelial cells can be activated and injured by CPB and ulinastatin pretreatment has protective effect.