Role of NF-kB in multiple organ dysfunction during acute obstructive cholangitis

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AIM: To elucidate the role of NF-kB activation in thedevelopment of multiple organ dysfunction (MOD) duringacute obstructive cholangitis (AOC) in rats.METHODS: Forty-two Wistar rats were divided into threegroups: the AOC group, the group of bile duct ligation (BDLgroup), and the sham operation group (SO group). All theanimals in the three groups were killed in the 6th and 48thhour after operation. Morphological changes of vital organswere observed under light and electron microscopy. NF-kBactivation was determined with Electrophoretic Mobility ShiftAssay (EMSA). Arterial blood gas analyses and the serumlevels of lactate dehydrogenase (LDH), alanineaminotransferase (ALT), blood urea nitrogen (BUN) andcreatinine were performed. The concentrations of TNF-αand IL-6 in plasma were also measured.RESULTS: The significant changes of histology andultrastructure of vital organs were observed in AOC group.By contrast, in BDL group, all the features of organs damagewere greatly reduced. Expression of NF-kB activation invarious tissues increased in AOC group when compared toother two groups. At 6 h, the arterial pH in three groupswas 7.52±0.01, 7.46±0.02, and 7.45±0.02, and the bloodpCO2 was 33.9±0.95 mmHg, 38.1±0.89 mmHg, 38.9±0).94mmHg, there was difference in three groups (P<0.05). At48 h, the blood pH values in three groups was 7.33±0.07,7.67±0.04, and 7.46±0.03, and blood HCO3- was 20.1±1.29mmol@L-1, 26.7±1.45 mmol@L-1 and 27.4±0.35 mmol@L-1, therewas also difference in three groups (P<0.05). In AOC group,Levels of LDH, ALT, BUN and creatinine were 16359.9±2278.8nkat@ L-1 5796.2±941.9 nkat@ L-1, 55.7±15.3 mg/dl, and 0.72±0.06 mg/dl, which were higher than in SO group (3739.1±570.L nkat@ L-1, 288.4±71.7 nkat@ L-1, 12.5±2.14 mg/dl, and0.47±0.03 mg/dl) (P<0.05). Levels of plasma TNF-α andIL-6 in AOC at 48 h were 429±56.62 ng@L-1 and 562±57 ng@L-1which increased greatly when compared to BDL group(139±L6 ng@L-1, 227±43 ng@L-1) and SO group (74±10 ng@L-1113±19 ng@L-1) (P<0.05).CONCLUSION: The pathological damages and the NF-kBactivation of many vital organs exised during AOC. Thesefindings have an important implication for the role of NF-kBactivation in MOD during AOC.
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