p38MAPK对猪MODS时内皮祖细胞的调控作用

The study of modulation of endothelial progenitor cells by p38 mitogen-activated protein kinase in porcine multiple organ dysfunction syndrome

目的探讨猪MODS时p38MAPK介导的TNF-α对内皮祖细胞(EPC)的调控作用,从EPC分化障碍的角度进一步研究创伤后MODS的发病机制。方法将20头家猪分为MODS组(M组)和对照组(C组),每组10头。采用"二次打击法"建立猪MODS模型,监测其各主要脏器功能的变化,体内用Western-blot法检测外周血单核细胞p38MAPK的磷酸化变化,用ELISA法测定外周血血浆TNF-α的浓度变化,流式细胞仪检测外周血EPC的数量变化。结果M组的MODS发生率明显高于C组,M组外周血单核细胞p38MAPK的磷酸化明显增强,TNF-α合成与分泌明显增加,外周血EPC数量与功能下降。结论外周血单核细胞p38MAPK的磷酸化使TNF-α的转录、合成增加,血浆TNF-α升高,使外周血中的EPC其数量与功能下降,炎症病理反应加重,可能是MODS的发病机制。

Objective To study the modulation of EPC by p38 mitogen activated protein kinase （MAPA） mediated TNF-α and the pathogenesis in multiple organ dysfunction syndrome. Methods Twenty porcines were divided into control （ C ） group and MODS （ M ） group. After establishment of MODS model, the fumction of main organs was determined. In vivo, the p38MAPK phosphorylation in the peripheral blood mononuclear cell was monitored with Western-blot, and TNF-α mRNA measured with RT-PCR, plasma TNF-α was measured with ELISA and EPC with FCM. Results The mobidity in group M was much higher than that in group C. In vivo the peripheral monocellular p38 MAPK phosphorylation was much more intense, the synthesis and secretion of TNF-α was markedly increased, and the quantity and function of EPC was markedly decreased. Conclusions The peripheral monocellular p38 MAPK phosphorylation can induce TNF-α mRNA transcription and increase its synthesis, and TNF-α of the peripheral blood mononuclear cell is increased, The increased TNF-α of the peripheral blood plasma could result in decrease of the quantity and function of EPC, and aggravate the inflammatory response of MODS, which could be the pathogenesis of MODS.