Abstract: Objective To investigate the molecular mechanisms of continuous venovenous hemofiltration (CVVH) combined
with ulinastatin (ULI) (CVVH-ULI) for the treatment of septic shock. Methods Human umbilical endothelial cells (HUVECs)
were incubated with serums isolated from normal healthy people (control), septic shock patients treated with conventional
therapy (CT) or treated with CVVH combined with ULI (CVVH-ULI). Endothelial permeability was evaluated by the leakage
of FITC-labeled albumin. The morphological changes of F-actin was evaluated by Rhodamine-phalloidin. The phosphorylated
levels of p38 were determined by Western blot. Cells were then treated with p38inhibitor (SB203580), or DMSO, followed by
incubation with serum from septic shock patients treated with conventional therapy. Endothelial permeability and F-actin
rearrangements were also evaluated as noted above. Results Serum from CT group increased endothelial permeability, F-actin
rearrangements, and phosphorylated levels of p38, which were inhibited by CVVH-ULI treatment. Moreover, in CT group, the
serum-induced endothelial hyperpermeability and F-actin rearrangements were inhibited by SB203580, the inhibitor of p38.
Conclusion CVVH combined with ulinastatin decreases endothelial hyperpermeability induced by septic shock through inhibiting
p38 MAPK pathways.