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核因子-κB在L-精氨酸所致小鼠急性水肿性胰腺炎模型早期发病中的作用探讨
Study on activation of the transcription factor NF-kappa B in the pancreas in the pathogenesis of L-arginine-induced acute edematous pancreatitis
【摘要】 目的 探讨核因子 κB(NF κB)DNA结合活性在小鼠急性水肿性胰腺炎 (AEP)病变胰腺组织早期中的变化及意义。方法 L 精氨酸腹腔注射诱导小鼠AEP ;对照组给予等量生理盐水。凝胶迁移率法 (EMSA)分析胰腺组织中NF κBDNA结合活性 ;碘比色法测定血清淀粉酶活力 ,放射免疫法测定血清白细胞介素 6(IL 6)、肿瘤坏死因子 α(TNF α)水平 ;留取胰腺组织分析病理形态学变化、进行病理评分 ;硫代巴比妥酸比色法检测胰腺组织 (丙二醛 )MDA含量 ,黄嘌呤氧化酶法测定胰腺组织 (超氧化物岐化酶 )SOD活力。结果 L 精氨酸腹腔注射后 ,小鼠出现AEP的改变 ;胰腺组织NF κB结合活性呈动态的改变 ,0 .5h时即开始增高 ,6h达到高峰 ,12h时仍高于NS组 (P <0 .0 1)。血清IL 6、TNF α水平 6h ,12h时均显著升高 ,高于NS组 (P <0 .0 1)。6h时组织中MDA含量明显升高并达到高峰 ,12h时仍高于NS组 (P <0 .0 1) ,12h时T SOD活力下降 ,与NS组相比 ,差异具有统计学意义 (P <0 .0 1)。结论 在L 精氨酸诱导的AEP早期 ,病变胰腺组织存在NF κBDNA结合活性的升高 ,NF κB参与L 精氨酸诱导的AEP的病情演变 ;机制可能与NF κB介导TNF α、IL 6,氧自由基产生及参与氧自由基对细胞膜脂质过氧化损伤有关 ;抑制NF κBDNA结合活性可能有助于改?
【Abstract】 Objective The aim of the present study was to explore the effect and signifisance of activation of the transcription factor NF kappa B in pathogenesis of L arginine induced acute edematous pancreatitis in mouse. Methods Acute edematous pancreatitis was induced in male mice by injecting L arginine intraperitoneally and the normal group just with normal saline. Mice were killed at various time points.Binding activity of NF kappB was detected with electrophoretic mobility shift assays. At the same time,levels of IL 6,TNF α and amylase in serum were studied.Levels of malonyl dialdehyde (MDA), superoxide dismutase (T SOD) in pancreatic tissue and histologic scores were measured. Results After injecting L arginine,acute edematous pancreatitis could be seen in model group but not in normal group .The binding activity of NF kappaB was increased with a dynamic curve.It began to increase at 0.5h point time and its peak was at 6h,then decreased but still significantly elevated at 12h versus NS Group(P<0.01). Levels of IL 6 ,TNF α and MDA significantly elevated at 6h, then decreased but still significantly elevated at 12h versus NS Group(P<0.01). The T SOD activity was significantly lower at 12h. Conclusions?The results suggest that NF kappa B activation is an important early event that may contribute to edema, inflammation and haemorrhage in acute pancreatitis. Oxygen derived free radicals and cytokines are involved in it.
- 【文献出处】 胃肠病学和肝病学杂志 ,Chinese Journal of Gastroenterology and Hepatology , 编辑部邮箱 ,2004年04期
- 【分类号】R576
- 【被引频次】17
- 【下载频次】131