连续性静脉-静脉血液透析滤过防治犬多器官功能障碍综合征  

Changes of LPS,CD14 and HMGB 1 in dogs with multiple organ dysfunction syndrome treated with continuous veno-venous haemodiafiltration

作　　者：刘新华[1] 米娜瓦尔.玉努斯 叶蕾[1] 吕雯雯[1] 刘红艳[1] 刘曾华[1] 陈继红[1] 

机构地区：[1]新疆医科大学第一附属医院肾病科,乌鲁木齐830054

出　　处：《肾脏病与透析肾移植杂志》2013年第4期340-345,共6页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：自治区科技支疆项目(201191160)

摘　　要：目的：观察连续性静脉-静脉血液透析滤过（CVVHDF）防治犬多器官功能障碍综合征（MODS）过程中内毒素、内毒素受体CD14和高迁移率族蛋白1（HMGB1）的变化. 方法：18只雄性Beagle犬随机分为正常对照组（n=6）、MODS组（n=6）和CVVHDF组（n=6）.采用失血性休克＋复苏灌注＋内毒素血症建立MODS模型[1],CVVHDF组在内毒素注射完毕后予CVVHDF治疗24h,MODS组不给CVVHDF治疗.术前（T1）、内毒素注射前（T2）、内毒素注射完毕后0h（T3）、3h（T4）、6h（T5）、9h（T6）、12h（T7）、18h（T8）及24h（T9）观察血浆内毒素、CD14及HMGB1变化,及各脏器组织CD14、HMGB1蛋白表达和病理学改变. 结果：CVVHDF治疗后,CVVHDF组血浆内毒素、CD14及HMGB1水平均逐渐下降,在T6-9时间点显著低于MODS组（P＜0.01）.CVVHDF组各组织中CD14、HMGB1蛋白表达均有所降低,其中,CVVHDF组肝脏及脑组织CD14蛋白表达显著低于MODS组（P＜0.05）,CVVHDF组肺脏、肾脏及脑组织HMGB1蛋白表达显著低于MODS组（P＜0.05）.CVVHDF治疗后肺脏、心脏、肝脏、肾脏及脑组织病理损伤明显减轻. 结论：过度炎症反应是MODS发生的本质原因之一,CVVHDF能够降低血循环中内毒素、CD14及HMGB1等炎症介质的峰值浓度,下调肺脏、心脏、肝脏、肾脏及脑组织中CD14、HMGB1蛋白表达,有效遏制过度的炎症反应,从而起到防治MODS的作用.Objective：To observe the changes of endotoxin （LPS）,its receptor CD14 and high mobility group-1 protein （HMGB1） in dogs with multiple organ dysfuncition syndrome （MODS） treated with continuous veno-venous haemodiafiltration （CVVHDF）.Methodology：Eighteen male Beagle dogs were randomly divided into normal control group （n =6）,MODS group （n =6） and HVH F group （n =6）.Hemorrhagic shock plus resuscitation and endotoxemia （two-hit） method was used to establish the dog MODS model.CVVHDF was performed about 24 hours after LPS injection in MODS dogs of CVVHDF group.Plasma LPS,CD14 and HMGB 1 were determined before operation （T1）,before LPS injection （T2） and Oh （T3）,3h （T4）,6h （T5）,9h （T6）,12h （T7）,18h （T8） and 24h （T9） after LPS injected.Protein express levels of CD14 and HMGB1 in main organ tissues were detected by fluorescent detection of Western blot.Pathological changes of main organ tissues were observed under the light microscopy.Results：Compared with the MODSgroup,plasma levels of LPS,CD14 and HMGB1 were significantly decreased in the CVVHDF group at T6-9 （P ＜ 0.01）.In CVVHDF group,protein express levels of CD14 and HMGB1 in main organ tissues were decreased.The CD14 protein express levels of liver and brain in CVVHDF groups were significantly lower than that in MODS group （P ＜ 0.05）.The HMGB1 protein express levels of lung,kidney and brain in CVVHDF groups were significantly lower than that in MODS group （P ＜ 0.05）.Pathological changes of major organs were improved in the CVVHDF group,as compared with animals in the MODS group.Conclusion：Excessive inflammatory response may be the essential pathogenesis of MODS.CVVHDF can cut down the peak value of inflammatory cytokines including LPS,CD14 and HMGB 1,down-regulate protein express levels of CD14 and HMGB 1 in main organ tissues,which can prevent and treat MODS.

关 键 词：多器官功能障碍综合征 血液透析滤过 内毒素 内毒素受体 高迁移率族蛋白1 

分 类 号：R459.5[医药卫生—治疗学]