内毒素及其受体CD14在高容量血液滤过防治多器官功能障碍综合征中的变化及意义

目的探讨高容量血液滤过（HVHF）防治多器官功能障碍综合征（MODS）中的内毒素及其受体CD14的变化和意义。方法建立二次打击猪MODS模型。19只猪完全随机分为MODS组（9只）及HVHF组（10只），MODS组实施失血性休克＋再灌注损伤＋内毒素复合因素，HVHF组实施失血性休克＋再灌注损伤＋内毒素复合因素＋高容量血液滤过，观察7d后处死动物。监测2组动物各主要脏器功能，用鲎试剂与鲎三肽的偶氮显色法定量测定2组动物血浆及HVHF组动物超滤液中内毒素的浓度变化，流式细胞仪检测外周血单核细胞CD14蛋白水平的表达变化。结果MODS组MODS发生率为88．9％（8／9），死亡率达77．8％（7／9），HVHF组MODS发生率为20％（2／10），死亡率为20％（2／10），显著低于MODS组（P〈0．01）。MODS组内毒素浓度在内毒素注射完毕后持续升高；HVHF组随着滤过的进行，内毒素浓度逐渐下降，各时间点与MODS组相比差异均有统计学意义。MODS组CD14的表达在内毒素开始注射后持续升高，注射至12h时表达水平达高峰，以后逐渐缓慢降低直至死亡前；HVHF组在滤过前CD14的表达变化同MODS组相似，但滤过24h后逐渐降低，各时间点与MODS组相比差异有统计学意义。结论内毒素及其受体CD14的变化可能在MODS的发病机制中起重要作用，早期HVHF可有效清除循环中高浓度的内毒素并下调CD14受体的表达水平，从而在早期和始动环节遏制失控性炎症反应的发生，限制MODS的发展。

Changes and significance of LPS and recognition receptor CD14 in prophylactic high volume hemofiltration treatment for multiple organ dysfunction syndrome

Objective To investigate the Changes and significance of LPS and recognition receptor CD14 in prophylactic high volume hemofiltration treatment for multiple organ dysfunction syndrome. Methods Double-hit porcine model of MOBS was duplicated in 19 pigs which were divided randomly into MOBS group (group M, n=9) and HVHF group(group HF, n=10). Group M was given compound factors including hemorrhagic shock, reperfu-sion injury and endotoxemia. Group HF was given prophylactic high-volume hemofiltration after endotoxemia. Major organs functions were monitored. Horseshoe crab reagent was used to detect the concentration of LPS in both group animal blood and the concentration of LPS in ultrafiltration at setting time points. The change of receptors CD14 pro-tein expression on monocytes was detected by flow cytometry. Results The morbidity of MOBS and mortality in group HF were 2/10 and 2/10 respectively, which was much lower than that in group M (8/9 and 7/9 respectively) (P<0.01). The concentration of blood LPS increased significantly after LPS injection and increased continually at every time point afterwards. Compared with group M, there was significant deviation at every time point after filtra-tion in group HF. There was no LPS in the ultrafihration in group HF. In group M, the expression intensity of CD14 protein kept increasing after the LPS injection and reached the peak at the 12th hour, and then decreased gradually. In group HF, the expression of CD14 was similar to that in group M before filtration, but was lower than group M 24h after the filtration and then decreased continually. Conclusions The changes of LPS and CD14 expression may play important role in the pathogenesis of MOBS. Earlier HVHF can remove the high concentration of blood LPS and down-regulate the expression of CD14. Accordingly it may inhibit the development of uncontrolled inflammation at earlier period and the development of MOBS.