高容量血液滤过防治MODS过程中内毒素受体及炎性细胞因子的变化及意义  

The change and significance of LPS recognition receptors and cytokines in prophylactic treatment for multiple organ dysfunction syndrome with high volume hemofiltration

作　　者：林富林[1] 沈贤[2] 柴琛[3] 申晓军[3] 鲁明良[1] 方国恩[3] 

机构地区：[1]中国人民解放军117医院大肠肛门病中心,浙江杭州310004 [2]温州医学院附属第一医院普外科,浙江温州325000 [3]第二军医大学长海医院普外科,上海200433

出　　处：《温州医学院学报》2011年第1期1-5,共5页Journal of Wenzhou Medical College

基　　金：全军医学科研"十五"计划重大课题(01Z057)

摘　　要：目的:探讨高容量血液滤过(high volume hemofiltration,HVHF)防治多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)过程中内毒素(LPS)受体及炎性细胞因子的变化及其关系。方法:建立二次打击(失血性休克+再灌注损伤+内毒素复合因素)猪MODS模型。19只猪随机分为MODS组(M组,9只)及HVHF组(HF组,10只)。M组为模型组,HF组在建模后实施高容量血液滤过,观察7 d后处死动物。流式细胞仪检测外周血单核细胞CD14、TLR4的表达变化,ELISA法检测血浆及滤液中TNFα、IL-10、IL-6浓度,并观察抗炎/促炎因子的比率变化。结果:HF组MODS发生率为2/10,死亡率为2/10,显著低于M组(P<0.01)。M组CD14、TLR4的表达在LPS注射后维持在较高水平;HF组CD14、TLR4的表达在滤过前同M组相似,但滤过后逐渐降低,各时间点与M组相比差异有统计学意义。滤过治疗开始后,TNFα、IL-10浓度开始下降,且明显低于治疗前水平,并维持在一个比较稳定的浓度,治疗后各时间点与M组相比差异有统计学意义;IL-6在治疗后虽有轻度上升,但治疗后各时间点较M组水平仍有显著下降;HF组IL-10/TNFα比率随治疗时间的延长保持在比较稳定的状态。结论:HVHF能有效降低血浆细胞因子水平,使得抗炎和促炎两方面趋于动态平衡;并可通过此途径下调CD14、TLR4受体的表达水平。Objective： To investigate the change and significance of LPS recognition receptors and cytokines in prophylactic treatment for multiple organ dysfunction syndrome with high volume hemofiltration.Methods： Double-hit porcine model（compound factors including hemorrhagic shock,reperfusion injury and endotoxemia） of MODS was duplicated in 19 pigs that were divided randomly into MODS group（group M,n =9）and HVHF group（group HF,n =10）.Group HF was given prophylactic high-volume hemofiltration after the model was duplicated.The animals were killed after 7 days.The change of receptors CD14,TLR4 protein expression on monocytes was detected by flow cytometry.The concentrations of TNFα,IL-10 and IL-6 in plasma and ultra-filtration were measured by ELISA.Results： The morbidity of MODS and mortality in group HF were 2/10 and 2/10 respectively,which was much lower than group M（P 0.01）.In group M,the expression intensity of CD14,TLR4 protein kept at high level after the LPS injection.In group HF,the expression of CD14,TLR4 was similar to that in group M before filtration,but decreased continually after filtration.There was significant deviation by compared with that of group M.Plasma concentration of TNFα,IL-10 began to descend at the early stage of treatment.It was obviously lower than pre-treatment level and maintained stable concentration during the procedure thereafter.The concentration of every post-treatment setting time point was much lower than that of the control group and had statistical significance.Plasma concentration of IL-6 at every post-treatment setting time point of group HF was significant lower than that of group M,although post-treatment level upgraded slightly than pre-treatment.The ratio of IL-10 to TNFα maintained stably during the course of HVHF.Conclusions： Earlier HVHF could cut down the plasma concentrations of proinflammatory cytokines（e.g.,TNFα） and make pro-inflammatory and anti-inflammatory cytokines to dynamics equilibrium,and may down-regulate the expression of CD1

关 键 词：多器官功能障碍综合征 血液滤过 细胞因子 TLR4 CD14 猪 动物模型 

分 类 号：R441.9[医药卫生—诊断学]