核因子-κB在急性梗阻性胆管炎多器官功能障碍中的作用
Role of NF-kB in multiple organ dysfunction during acute obstructive cholangitis.
作者信息
Tu Bin, Gong Jian-Ping, Feng Hu-Yi, Wu Chuan-Xin, Shi Yu-Jun, Li Xu-Hong, Peng Yong, Liu Chang-An, Li Sheng-Wei
机构信息
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.
出版信息
World J Gastroenterol. 2003 Jan;9(1):179-83. doi: 10.3748/wjg.v9.i1.179.
AIM
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).
CONCLUSION
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.
目的
阐明核因子-κB（NF-κB）激活在大鼠急性梗阻性胆管炎（AOC）期间多器官功能障碍（MOD）发生发展中的作用。
方法
42只Wistar大鼠分为三组：AOC组、胆管结扎组（BDL组）和假手术组（SO组）。三组所有动物均在术后第6小时和第48小时处死。在光镜和电镜下观察重要脏器的形态学变化。采用电泳迁移率变动分析（EMSA）测定NF-κB激活情况。进行动脉血气分析以及测定血清乳酸脱氢酶（LDH）、丙氨酸氨基转移酶（ALT）、血尿素氮（BUN）和肌酐水平。同时检测血浆中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的浓度。
结果
AOC组重要脏器的组织学和超微结构有显著变化。相比之下，BDL组器官损伤的所有特征均明显减轻。与其他两组相比，AOC组各组织中NF-κB激活的表达增加。术后6小时，三组动脉血pH值分别为7.52±0.01、7.46±0.02和7.45±0.02，血二氧化碳分压（pCO₂）分别为33.9±0.95 mmHg、38.1±0.89 mmHg、38.9±0.94 mmHg，三组间存在差异（P<0.05）。术后48小时，三组血pH值分别为7.33±0.07、7.67±0.04和7.46±0.03，血碳酸氢根（HCO₃⁻）分别为20.1±1.29 mmol·L⁻¹、26.7±1.45 mmol·L⁻¹和27.4±0.35 mmol·L⁻¹，三组间也存在差异（P<0.05）。AOC组LDH、ALT、BUN和肌酐水平分别为16359.9±2278.8 nkat·L⁻¹、5796.2±941.9 nkat·L⁻¹、55.7±15.3 mg/dl和0.72±0.06 mg/dl，高于SO组（3739.1±570.1 nkat·L⁻¹、288.4±71.7 nkat·L⁻¹、12.5±2.14 mg/dl和0.47±0.03 mg/dl）（P<0.05）。AOC组术后48小时血浆TNF-α和IL-6水平分别为429±56.62 ng·L⁻¹和562±57 ng·L⁻¹，与BDL组（139±16 ng·L⁻¹、227±43 ng·L⁻¹）和SO组（74±10 ng·L⁻¹、113±19 ng·L⁻¹）相比显著升高（P<0.05）。
结论
AOC期间多个重要脏器出现病理损伤及NF-κB激活。这些发现对NF-κB激活在AOC期间MOD中的作用具有重要意义。
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