Improving RhoA-mediated intestinal epithelial permeability by continuous blood purification in patients with severe acute pancreatitis.

Background: Early dysfunction of the intestinal mucosal barrier contributes to increasing intestinal permeability. It may play an important role in the pathophysiology of severe acute pancreatitis (SAP). A rising number of clinical data have showed that continuous blood purification (CBP) may improve the prognosis of SAP. However, the therapeutic effects of CBP on intestinal epithelial permeability have been rarely reported. Methods: Intestinal epithelial monolayer (Caco-2) was incubated with serum samples collected at specific time points from SAP patients during CBP. Changes in intestinal epithelial monolayer permeability and configuration, and levels of cellular tight junction structural proteins including occludin and ZO-1, and RhoA mRNA expression level were recorded, respectively. In addition, serum tumor necrosis factor-alpha (TNF-alpha) levels at specific time points during CBP were determined. Results: Before CBP initiation, intestinal epithelial permeability was increased and tight junction structural protein level was decreased and reorganized, but RhoA mRNA expression and serum TNF-alpha were increased. However, after CBP treatment, intestinal epithelial permeability was reduced and tight junction protein levels were increased, with reorganization attenuated. Meanwhile, RhoA mRNA expression and serum TNF-alpha level was decreased. Conclusions: After CBP treatment, intestinal epithelial permeability was reduced by increasing occludin and ZO-1 protein level and attenuating reorganization. This beneficial effect of CBP on intestinal epithelial permeability is associated with down-regulation of RhoA mRNA expression, and it may be related to the removal of TNF-alpha by CBP.