聚偏氟乙烯-丝氨酸新型吸附膜血液灌流对猪脓毒血症肺损伤的影响

Effect of hemoperfusion with adsorbents containing ser ligand for endotoxin removal on lung injuries in a porcine model of endotoxemia

目的 研究应用聚偏氟乙烯（PVDF）-丝氨酸（Ser）新型吸附膜进行血液灌流治疗对猪脓毒血症肺损伤的影响及探讨可能存在的机制.方法 将13只雄性大长种家猪随机（随机数字法）分为实验组（n=7）和对照组（n=6）.采用内毒素（LPS）1 μg（kg·h）静脉泵入2 h复制脓毒血症模型.实验组脓毒血症模型制作完成后1 h开始应用PVDF-Ser吸附膜进行血液灌流2 h;对照组应用空载体血液灌流对照试验.监测血浆TNF-α和IL-6水平;血液灌流结束处死动物后检测血管外肺水、肺泡毛细血管通透性、肺组织TNF-α和IL-6水平、丙二醛（MDA）、谷光苷肽（GSH）、髓过氧化物酶（MPO）活性并进行肺组织病理学和MPO免疫组化分析.数据处理采用方差分析.结果 静脉泵入LPS后,两组均表现为血管外肺水和肺泡毛细血管通透性增加,肺组织病理学损伤、血浆及肺组织炎症因子水平和氧化应激水平上调.与对照组相比,PVDF-Ser血液灌流能显著改善血管外肺水、肺泡毛细血管通透性以及肺组织病理学损伤（P＜0.05）,下调血清IL-6（P＜0.05）、肺组织TNF-α（P＜0.01）以及氧化应激水平（P＜0.05）.血清TNF-α水平两组间差异无统计学意义.结论 应用PVDF-Ser吸附膜进行血液灌流,可以降低炎症反应和氧化应激,改善肺损伤,具有潜在的临床应用价值.

Objective A new type adsorbent for removal of bacterial ET was prepared by immobilizing L-serine covalently onto polyvinylidene difluoride membrane （PVDF-Ser） to study the effect of hemoperfusion on sepsis induced lung injuries in a pig model. Method Endotoxemia were induced in thirteen pigs by injecting endotoxin （1 μg/（kg·h） ） intravenously for 2 h. One hour later, the pigs were treated with absorber of PVDF-Ser volumn （group hemoperfusion） or empty adsorber （group control） for 2 h. Extravascular lung water indexed to body weight and alveolar capillary permeability, levels of serum endotoxin, tumor necrosis factor-α, interleukin-6, malondialdehyde, glutathione, myeloperoxidase activity, and lung histological changes and myeloperoxidase immunohistochemical analysis were measured. Results Hemoperfusion treatment with PVDF-Ser volumn significantly improved extravascular lung water, pulmonary alveolar capillary permeability and lung injuries （ P 〈 0. 05）. In addition, hemoperfusion attenuated both serum and pulmonary cytokines, and decreased lung malondialdehyde and myeloperoxidase levels （ P 〈 0. 05）. Conclusions Hemoperfusion with the adsorber of PVDF-Ser volumn effectively reduced inflammatory responses and improved lung injuries and oxidative stress in endotoxemia. It has a high potential of clinical application for treatment of patients with severe sepsis.