Effects of gut barrier dysfunction and NF-κB activation on aggravating mechanism of severe acute pancreatitis

To study the effects of gut-derived endotoxin translocation and NF-kappa B activation on the aggravating mechanism of severe acute pancreatitis (SAP) and of treatment with pyrrolidine dithiocarbamate (PDTC) on rats with SAP. SD rats were randomly divided into sham operation group (SO), SAP group, SAP + lipopolysaccharide(LPS) group, pyrrolidine dithiocarbamate (PDTC) treatment group and LPS group. Biochemical parameters and cytokines were examined in the serum. Multiple organs pathological slices were examined. Expression of NF-kappa B mRNA in the liver tissue was detected by RT-PCR. Activation of NF-kappa B by the method of streptomycin avidin-peroxidase (SP) and expression of NF-kappa B p65 protein and its binding activity were analyzed by Western blot and electrophoretic mobidity shift assay (EMSA). Compared with sham operation group, the concentration of TNF-alpha, alanine aminotransferase (ALT), and diamine oxidase (DAO) in serum significantly increased in SAP + LPS group (P < 0.05). Pathological changes were markedly observed in tissues and the expression of NF-kappa B mRNA in the liver significantly increased (P < 0.05) also, the activation of NF-kappa B and binding activity of NF-kappa B p65 protein in the liver markedly increased (P < 0.01) in SAP + LPS group. Treatment with PDTC markedly reduced concentration of ALT, DAO and TNF-alpha, and the expression of NF-kappa B, and the pathologic scores, as well as significantly decreased the expression of NF-kappa B p65 protein. The activation and overexpression of NF-kappa B may participate in the aggravating mechanism of SAP. Treatment with PDTC has a protective effect on multiple organs damage in SAP.