Role of NF-kB in multiple organ dysfunction during acute obstructive cholangitis.
OBJECTIVE
To elucidate the role of NF-kB activation in the development of multiple organ dysfunction (MOD) during acute obstructive cholangitis (AOC) in rats.


METHODS
Forty-two Wistar rats were divided into three groups: the AOC group, the group of bile duct ligation (BDL group), and the sham operation group (SO group). All the animals in the three groups were killed in the 6th and 48th hour after operation. Morphological changes of vital organs were observed under light and electron microscopy. NF-kB activation was determined with Electrophoretic Mobility Shift Assay (EMSA). Arterial blood gas analyses and the serum levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine were performed. The concentrations of TNF-alpha and IL-6 in plasma were also measured.


RESULTS
The significant changes of histology and ultrastructure of vital organs were observed in AOC group. By contrast, in BDL group, all the features of organs damage were greatly reduced. Expression of NF-kB activation in various tissues increased in AOC group when compared to other two 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 blood pCO(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 was 7.33+/-0.07, 7.67+/-0.04, and 7.46+/-0.03, and blood HCO(3)(-) was 20.1+/-1.29 mmol x L(-1), 26.7+/-1.45 mmol x L(-1) and 27.4+/-0.35 mmol x L(-1), there was also difference in three groups (P<0.05). In AOC group, Levels of LDH, ALT, BUN and creatinine were 1,6359.9+/-2,278.8 nkat x L(-1), 5,796.2+/-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 (3,739.1+/- 570.1 nkat x L(-1), 288.4+/-71.7 nkat x L(-1), 12.5+/-2.14 mg/dl, and 0.47+/-0.03 mg/dl) (P<0.05). Levels of plasma TNF-alpha and IL-6 in AOC at 48 h were 429+/-56.62 ng x L(-1) and 562+/-57 ng x L(-1), which increased greatly when compared to BDL group (139+/-16 ng x L(-1), 227+/-43 ng x L(-1)) and SO group (74+/-10 ng x L(-1), 113+/-19 ng x L(-1)) (P<0.05).


CONCLUSIONS
The pathological damages and the NF-kB activation of many vital organs excised during AOC. These findings have an important implication for the role of NF-kB activation in MOD during AOC.
Tu
Bin
B
Department of General Surgery, the Second College of Clinical Medicine and the Second Affiliated Hospital of Chongqing University of Medical Science, 74 Linjiang Road, Chongqing 400010, China.
Gong
Jian-Ping
JP
Feng
Hu-Yi
HY
Wu
Chuan-Xin
CX
Shi
Yu-Jun
YJ
Li
Xu-Hong
XH
Peng
Yong
Y
Liu
Chang-An
CA
Li
Sheng-Wei
SW
D000208:Acute Disease; D000818:Animals; D001774:Blood Chemical Analysis; D002761:Cholangitis / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007684:Kidney Tubules / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D009102:Multiple Organ Failure / Q000378:metabolism*; D009186:Myelin Sheath / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha