Intestinal mucosal barrier dysfunction in SAP patients with MODS ameliorated by continuous blood purification

Abstract

Background: Dysfunction of the intestinal mucosal barrier plays an important role in the pathophysiology of severe acute pancreatitis (SAP). Continuous blood purification (CBP) has been shown to improve the prognosis of SAP patients. In order to investigate the effect of CBP on intestinal mucosal barrier dysfunction in SAP patients with MODS, we conducted in vivo and in vitro experiments to explore the underlying mechanisms. Methods: The markers for the assessment of intestinal mucosal barrier function including serum diamine oxidase (DAO), endotoxin and intestinal epithelial monolayer permeability were detected during CBP therapy. The distribution and expression of cytoskeleton protein F-actin and tight junction proteins claudin-1 were observed. In addition, Rho kinase (ROCK) mRNA expression and serum tumor necrosis factor-alpha (TNF-α) levels during CBP were determined. Results: SAP patients with MODS had increased levels of serum DAO, endotoxin and intestinal epithelial monolayer permeability when compared with normal controls. While the distribution of F-actin and claudin-1 was rearranged, and the expression of claudin-1 significantly decreased, but F-actin had no change. Meanwhile, ROCK mRNA expression and serum TNF-α level were increased. However, after CBP treatment, levels of serum DAO, endotoxin and intestinal epithelial monolayer permeability decreased. The F-actin and claudin-1 reorganization attenuated and the expression of claudin-1 increased. At the same time, ROCK mRNA expression and serum TNF-α level were decreased. Conclusions: CBP can effectively improve intestinal mucosal barrier dysfunction. The beneficial effect is associated with the improvement of cytoskeleton and tight junction proteins in stability by downregulation of ROCK mRNA expression through the removal of excess proinflammatory factors.