连续性血液透析滤过对多器官功能障碍犬血浆炎性相关介质的影响

Effects of continuous venovenous hemodiafdtration on plasma LPS, IL-llS, IL-4, HMGB-1 in multiple organ dysfunction syndrome dogs

目的观察连续性血液透析滤过（CVVHDF）对多器官功能障碍综合征（MODS）犬血浆脂多糖（LPS）、白细胞介素（IL）lβ、IL-4、高迁移率族蛋白1（HMGB-1）的影响，探讨CVVHDF的治疗机制。方法经失血性休克＋复苏灌注＋内毒素静脉滴入建立犬MODS模型，按随机数字表法分为CVVHDF组（n=6）和MODS组（n=6）。内毒素静脉滴入完毕后CVVHDF组接受CVVHDF治疗24h；MODS组未接受CVVHDF治疗。测定各时间点[术前，内毒素静脉滴人前，内毒素静脉滴人完毕后0、3、6、9、12、18、24h]lfil浆及超滤液LPS、IL-1β、IL-4、HMGB-1浓度，计算筛选系数（sc）。结果与MODS组相比，CVVHDF组血浆LPS、IL-lp、IL-4、HMGB-1浓度显著降低，在内毒素静脉滴入完毕后9、12、18、24h差异有统计学意义（P〈0．05）。在超滤液中可以检测出一定浓度的IL．1B、IL．4、HMGB．1，其筛选系数sc分别为0．60±0．12、0．83±0．11、0．70±0．09，而超滤液中未能检测出LPS，其sc为0。CVVHDF组肺脏、肾脏的损害程度较MODS组明显减轻。结论CVVHDF可以清除MODS相关炎性介质和抗炎介质，阻断细胞因子网络的恶性循环，减轻机体的损害程度，有效地救治MODS。

Objective To investigate the effects of continuous venovenous hemodiafiltration （CVVHDF） on plasma lipopolysaccharide （LPS）, interleukin（IL） 1β, IL-4, high mobility group box 1 （HMGB-1） in multiple organ dysfunction syndrome （MODS） dogs, to explore the therapeutic mechnism of CVVHDF. Methods Dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model, then they were randomly divided into 2 groups： CVVHDF group （n=6） and MODS group （n=6）. After endotoxin injection completed, the CVVHDF group received CVVHDF treatment for 24 h; MODS group did not receive CVVHDF treatment. The LPS, IL-113, IL-4, HMGB-1 levels in plasma and uhrafihrate were measured at different time points（before operation, before intravenous infusion of endotoxin, 0 h, 3 h, 6 h, 9 h, 12 h, 18 h, 24 h after intravenous infusion completion of endotoxin）, then the sieving coefficient （SC） was calculated. Results Compared with MODS group, the LPS, IL-113, IL-4, HMGB-1 levels in plasma were significantly decreased in the CVVHDF group at 9 h, 12 h, 18 h, 24 h （P 〈 0.05）. Some concentration of IL-113, IL-4 and HMGB-1 was detected in the ultrafiltrate, the SC for IL-113, IL-4 and HMGB-1 was 0.60±0.12, 0.83±0.11, 0.70±0.09 respectively, and LPS could not bedetected in the uhrafihrate, its SC was 0. After treatment, the damage level of lung and renal had been significantly reduced in CVVHDF group. Conclusion CVVHDF can effectively reduce the levels of pro-inflammatory mediator and anti-inflammatory cytokine related to MODS, cut off the vicious circle of cytokine network and reduce the damage level of organism in the treatment of MODS.