白介素-1β在猪多器官功能障碍综合征中对内皮祖细胞的调控

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

目的 探讨猪多器官功能障碍综合征（MODS）中p38MAPK介导的白介素（IL）-1β对内皮祖细胞（EPC）的数量与功能的调控，从血管内皮祖细胞分化障碍来研究创伤后MODS的发病机制。方法将30头家猪随机分为MODS组（n=15，M组）、对照组（n=15，C组），采用失血性休克与内毒素血症的“二次打击法”建立猪MODS模型，在体内Western—blot法检测外周血单核细胞p38MAPK的磷酸化变化；ELISA法测定外周血血浆IL-1β的浓度变化；流式细胞仪检测外周血EPC数量的变化；采用x^2检验比较M组与C组的MODS发生率，采用成组t检验比较M组与C组的p38MAPK的磷酸化变化、外周血血浆IL-1β的浓度变化与外周血EPC数量的变化。结果在MODS中外周血单核细胞p38MAPK的磷酸化增强，导致其外周血IL-1β浓度升高，从而使得外周血EPC数量下降，M组MODS的发生率均明显高于C组（P〈0．01）；M组的外周血单核细胞p38MAPK的磷酸化与外周血血浆IL-1β的浓度明显高于C组（P〈0．01）；M组外周血EPC数量明显低于C组（P〈0．01）。结论在猪MODS的发病机制中，外周血单核细胞内的p38MAPK的磷酸化使血浆IL-1β浓度升高，使EPC的数量下降，致使MODS的炎症反应加重。

Objective To investigate the modulation of EPCs by interleukin 1β （IL-1β） and p38 mitogen activated protein kinase （p38MAPK） and the pathogenesis resulting from their dysdifferentiation after trauma. Method Thirty pigs were divided into a control group （n = 15） and a multiple organ dysfunction syndrome （MODS） group （ n = 15）, the latter of which were subjected to a ＂two-hit＂ injury including hemorrhagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentrations of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student＇ s t test. Results The level of p38MAPK phosphorylation was more augmented and the concentration of IL-1β higher in peripheral blood mononuclear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the number of EPC conspicuously decreased in the peripheral blood （P 〈 0.01 ）. The morbidity rate in the MODS group was much higher than that in the control group （ P 〈 0.01 ）. There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C （P 〈 0.01 ）. Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phosphorylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflammatory reaction in MODS.