• Ying-jian Liang, Xiao-chun Ma, and Xin Li.
• Intensive Care Unit, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China.
• Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2010 Sep 1;22(9):528-32.

ObjectiveTo determine the activation status of p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor-ΚB (NF-ΚB) in coagulation disorders due to endothelial injury induced by sepsis.MethodsHuman umbilical vein endothelial cells (HUVECs) were exposed to plasma obtained from 22 patients suffering from sepsis. Plasma was also obtained from 8 healthy individuals to serve as negative control, and tumor necrosis factor-α (TNF-α) was used as positive control. Phosphorylation and activity of p38MAPK and NF-ΚB were determined with enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunofluorescence assay.ResultsThe level of TNF-α (ng/L) in sepsis plasma was significantly higher than that in healthy plasma (155.68±89.74 vs. 5.00±0.47, P <0.01). Compared with healthy plasma in 20% concentration it was found when HUVECs were treated with sepsis plasma in 20% concentration, tissue factor (TF, μg/L) reached the peak at 180 minutes (5.87±0.14 vs. 1.25±0.11, P <0.01), von Willebrand factor (vWF, μg/L) reached the peak at 120 minutes (9.59±0.07 vs. 3.59±0.06, P <0.01), then they began to decline. When HUVECs were treated with sepsis plasma in 20% concentration increased phosphorylation and activity of p38MAPK and NF-ΚB, phosphorylation of p38MAPK occurred before phosphorylation of NF-ΚB (2 minutes vs. 5 minutes). When the inhibitor of p38MAPK (SB239063) was added, NF-ΚB phosphorylation (activation) and NF-ΚB nuclear translocation were inhibited.ConclusionThis study demonstrates that p38MAPK/NF-ΚB transduction pathway plays an important role in septic coagulopathy.

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