[Modulation of endothelial progenitor cells by tumor necrosis factor-α in multiple organ dysfunction syndrome in...

To study the modulation in number and function of endothelial progenitor cell (EPC) in multiple organ dysfunction syndrome (MODS) after trauma in swine, and to investigate its pathogenesis.

Forty pigs were divided into sham group and MODS group (each, n=20). The model of MODS of "two-hit" injury, namely hemorrhagic shock and endotoxemia, was reproduced. The peripheral blood was collected before hemorrhage (T1) and endotoxin injection (T2), and 1 hour (T3), 24 hours (T4), 48 hours (T5) after endotoxin injection. Phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK ) in mononuclear cell was determined by Western Blot, the content of tumor necrosis factor-α (TNF-α) was determined with enzyme linked immunosorbent assay (ELISA), and the number of EPC was determined with flow cytometry.

Model of MODS was successfully reproduced in 17 pigs. In model group, the expression of p-p38MAPK (A value) peaked at T3 (4.83±0.52), and gradually declined at T4 and T5 (4.36±0.43, 1.93±0.33), and the expression of p-p38MAPK at T3-T5 was significantly higher than that at T1 (1.00±0.22, all P<0.01). The plasma concentration of TNF-α (ng/L) at T3 in MODS group was obviously elevated compared with that of sham group (532.43±52.17 vs. 129.03±20.45, t=31.163, P<0.001), and it peaked at T3, it then gradually lowered, and it was significantly higher at T4 and T5 than that in sham group (T4: 398.93±35.75 vs. 131.12±29.53, t=26.562, P<0.001; T5: 287.48±27.26 vs. 126.44±26.96, t=17.861, P<0.001). The number of EPC (×10(7)/L) was apparently increased in MODS group at T3 compared with sham group (4.832±0.624 vs. 3.545±0.363, t=9.542, P<0.001), and it peaked at T3, then gradually decreased, and the number of EPC at T4 and T5 was significantly lower than that in sham group (T4: 2.628±0.627 vs. 3.442±0.325, t=5.043, P<0.001; T5: 2.203±0.711 vs. 3.471±0.323, t=2.972, P<0.001).

Phosphorylation of p38MAPK could increase the plasma concentration of TNF-αand decrease the quantity of EPC in MODS,which may be one of the mechanisms of MODS.