[Mechanism of continuous venovenous hemofiltration combined with ulinastatin for the treatment of septic shock].
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.


CONCLUSIONS
CVVH combined with ulinastatin decreases endothelial hyperpermeability induced by septic shock through inhibiting p38 MAPK pathways.
Department of Pathophysiology of Southern Medical University, Key Laboratory of Shock and Microcirculation of Guangdong Province,Guangzhou 510515, China. E-mail: lanblue@smu.edu.cn.
Xiaohua
X
Guo
Zhenglian
Z
Wang
Yanan
Y
Liu
Qiulin
Q
Xu
Lei
L
Su
Fan
F
Wu
D000199:Actins / Q000378:metabolism; D002478:Cells, Cultured; D006023:Glycoproteins / Q000627:therapeutic use*; D006440:Hemofiltration / Q000379:methods*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D007093:Imidazoles; D020935:MAP Kinase Signaling System; D011725:Pyridines; D012772:Shock, Septic / Q000628:therapy*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000199:Actins; D006023:Glycoproteins; D007093:Imidazoles; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C028665:urinastatin; C093642:SB 203580