[Effect of ubiquitin-proteasome pathway on inflammatory reaction in intestine and its barrier function in rats with postburn sepsis].

OBJECTIVE: To study the effect of ubiquitin-proteasome pathway inhibition on intestinal nuclear factor-KappaB (NF-KappaB) activity and tumor necrosis factor-alpha (TNF-alpha) release as well as plasma diamine oxidase (DAO) activity in rats with postburn sepsis. METHODS: Rats were subjected to 30% total body surface area (TBSA) full-thickness scald injury, followed by intraperitoneal injection of lipopolysaccharide (LPS) to mimic postburn sepsis. Sixty Wistar rats were randomly divided into normal control group, sepsis group, sepsis with proteasome inhibitor N-Acetyl leucinyl leucinyl norleucinal (ALLN) treatment group and sepsis with NF-KappaB inhibitor pyrrolidine dithiocarbamate (PDTC) treatment group. NF-KappaB activity, TNF-alpha protein content, and plasma DAO activity were determined by electrophoretic mobility shift assay (EMSA), enzyme-linked immunosorbent assay (ELISA), and spectrophotometric method, respectively. RESULTS: The results showed that NF-KappaB activity was markedly activated and reached its peak 1 hour after scalding and injection of LPS in each group (all P<0.01), then reduced gradually. Both ALLN and PDTC could decrease intestinal NF-KappaB activity at 1 hour and 2 hours after injury. TNF-alpha release was reduced by ALLN at 1 hour after injury (P<0.01). Plasma DAO activity was significantly elevated after scalding and injection of LPS (P<0.01). Pretreatment with PDTC or ALLN could not lower the activity of DAO. CONCLUSION: The results suggest that early treatment with inhibitor of ubiquitin-proteasome pathway might decrease the intestinal inflammatory reaction, but exert no effect on intestinal barrier function in rats with postburn sepsis.