| Objective: The present study was performed to (l)investigate the activation of NF-KB in burn sepsis rats and it's influence on secretion of cytokine and organs' injury; (2)clarify the effect of NF-кB on burn sepsis; (3)primarily study the effect of ubiquitiaTproteasome pathway inhibition _on NF-KB activation, the pathogenesis of burn sepsis and subsequent multiple organ dysfunction syndrome (MODS); (4)investigate changes in proteolytic rate of skeletal muscle in burn sepsis rats; (5)study the effect of NF-кB inhibitor PDTC or proteasome inhibitor ALLN on proteolytic rate of skeletal muscle respectively; (6)elucidate the role of NF-кB and ubiquitin-proteasome pathway in muscle wasting during burn sepsis.Methods: Rats were subjected to 30% full-thickness scald injury and lipopolysaccharide (LPS)(4mg/kg) given intraperitoneally to mimic early burn sepsis. Two hundred and ten rats were randomly divided into four groups as follows: normal control group, fifteen rats served as controls; burn sepsis group, being further divided respectively into 1h, 2h, 6h, 12h and 24h subgroups after scalding and injection of LPS, n=75; PDTC group, intraperitoneal injection of PDTC at a dose of 200mg/kg at Ih prior to scalding and injection of LPS, being further divided respectively into Ih, 2h, 6h and 12h subgroups after scalding and injection of LPS, n=60; ALLN group, intraperitoneal injection of ALLN at a dose of 30mg/kg at Ih prior to scalding and injection of LPS, being further divided respectively into Ih, 2h, 6h and 12h subgroups after scalding and injection of LPS, n=60. At serial time points in each group, animals were euthanized. Blood, muscle and tissue samplesfrom livers, lungs, kidneys and small intestines were harvested. NF-кB activation, IкB-a expression, tumor necrosis factor-α (TNF-α) protein expression and proteolytic rate of skeletal muscle were determined by electrophoretic mobility shift assay (EMSA), Western blot analysis, enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), respectively. The major organ functional indices-serum AST, ALT, BUN and Cr contents, were measured with automatic biochemistry analyzer.Results: 1. Dynamic changes in NF-кB activation in burn sepsis rats and the effect of PDTC or ALLN on it NF-KB activation in livers, lungs, kidneys and small intestines was detectable at very low levels in normal control, markedly increased and reached it's peak at 1h after scalding and injection of LPS (P<0.01). After that, the NF-KB activation was reduced gradually, but the level was still significantly higher than that of normal control at 24h (P<0.01 or P<0.05). PDTC or ALLN could suppress NF-кB activation in different organs to some extent. 2. Dynamic changes in InB-α expression in the liver in burn sepsis rats and the effect of ALLN on it IкB-α expression in the liver reduced evidently at Ih after scalding and injection of LPS (P<0.05), then it gradually recovered to the normal level 24h after injury. The decrease of IicB-a at Ih was markedly suppressed by treatment with ALLN prior to scalding and injection of LPS, but not at 2h. 3. Changes in TNF-a expression in the organs or in plasma in burn sepsis rats and the effect of PDTC or ALLN on it TNF-a protein in the organs or in plasma was markedly increased at 1h and 2h after scalding and injection of LPS (P<0.01). However, pretreatment with PDTC or ALLN could reduce the organs and plasma TNF-α level to some extent. 4. Changes in pulmonary MPO activity and the effect of PDTC or ALLN on it Pulmonary MPO activity was significantly elevated at 2h and 6h after scalding and injection of LPS (P<0.01). Pretreatment with PDTC or ALLN could markedly lower the MPOactivity at 2h and 6h (P<0.01). 5. Changes in serum biochemical indices reflecting hepatic and renal function in burn sepsis rats and the effect of PDTC or ALLN on it Serum ALT, AST, BUN and Cr concentrations were statistically elevated at 2h and 6h after scalding and injection of LPS. Pretreated with ALLN or PDTC could significantly decreas...
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