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

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:jack0418
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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-κBactivation 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-κB 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 bloodpCO_2 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 HCO_3~- 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±570.1 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~(-1),which increased greatly when compared to BDL group(139±16 ng·L~(-1),227±43 ng·L~(-1))and SO group(74±10 ng·L~(-1),113±19 ng·L~(-1))(P<0.05).CONCLUSION:The pathological damages and the NF-κBactivation of many vital organs exised during AOC.These findings have an important implication for the role of NF-κBactivation in MOD during AOC. AIM: To elucidate the role of NF-kB activation in the development of multiple organ dysfunction (MOD) duringacute obstructive cholangitis (AOC) in rats. METHODS: Forty-two Wistar rats were divided into three groups: the AOC group, the group of bile duct Ligation (BDLgroup), and the sham operation group (SO group). All the animals in the three groups were killed in the 6th and 48th hours after operation. Morphological changes of vital organs were observed under light and electron microscopy. NF-κB activation was determined with Electrophoretic Mobility Shift Assay (EMSA). Arterial blood gas analyzes and the serum levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine were performed. These concentrations of TNF-α and IL-6 in plasma were also measured. RESULTS: The significant changes in 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-κB activation inv arious tissues increased in AOC group when compared to two other groups. At 6 h, the arterial pH in three groups was 7.52 ± 0.01, 7.46 ± 0.02, and 7.45 ± 0.02, and the bloodpCO 2 was 33.9 ± 0.95 mmHg, 38.1 ± 0.89 mmHg, 38.9 ± 0.94 mmHg, there was difference in three groups (P <0.05) .At 48 h, the blood pH values ​​in three groups were 7.33 ± 0.07, 7.67 ± 0.04, and 7.46 ± 0.03, and blood HCO 3 ~ was 20.1 ± 1.29 mmol There were also differences in three groups (P <0.05). In AOC group, Levels of L (-1), 26.7 ± 1.45 mmol·L -1 and 27.4 ± 0.35 mmol·L -1 LDH, ALT, BUN and creatinine were 16359.9 ± 2278.8 nkat · 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 ± 570.1 nkat · L -1, 288.4 ± 71.7 nkat · L -1, 12.5 ± 2.14 mg / dl, and 0.47 ± 0.03 mg / dl) (P <0.05) .Levels of plasma TNF-α and IL-6 in AOC at 48 h were 429 ± 56.62 ng · L -1 and 562 ± 57 ng · L -1, which increased greatly compared to BDL group (139 ± 16 ng · L -1 and 227 ± 43 ng · L -1) and SO group (74 ± 10 ng · L -1), 113 ± 19 n g · L -1 (P <0.05) .CONCLUSION: The pathologyical damages and the NF-κBactivation of many vital organs exised during AOC. The findings have an important implication for the role of NF-κB activation in MOD during AOC.
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