核因子-κB在重症急性胰腺炎肺损伤发病机制中的作用

The Role of Nuclear Factor-kappa B in the Pathogenesis of Severe Acute Pancreatitis-Associted Lung Injury

目的 探讨校因子-κB（nuclear factor-kappa B,NF-κB）在重症急性胰腺炎（SAP）肺损伤发病机制中的作用。方法 66只雌性Wistar大鼠随机分为正常组、SAP组、PDTC（二硫代氨基甲酸吡咯烷）预处理组三组。SAP模型采用5％的牛磺胆酸钠1ml/kg胰胆管内逆行注射方法建立。PDTC预处理组在建立SAP模型前1h腹腔内注射PDTC 100ml/kg。后两组分别在3、6、12h三个时相点将动物处死后（各10只）,留取肺组织。应用SP免疫组化方法检测SAP肺组织NF-κB表达情况,运用RT-PCR的方法检测肺组织TNFα、IL-6、ICAM-1mRNA的表达,并测定肺组织湿/干比值作为肺损伤的指标。结果 SAP组肺组织湿/干比值除3h与正常组相比无差异外,其余各组与正常对照组之间有显著性差异（P<0.05）,肺组织内可见NF-κB活化的中性粒细胞浸润,且肺组织TNFα、IL-6、ICAM-1mRNA表达增加。PDTC预处理组肺组织湿/干比值明显降低,NF-κB活化的中性粒细胞明显减少,TNFα、IL-6、ICAM-1 mRNA表达水平显著降低。结论 SAP时存在肺损伤,肺组织NF-κB活化并通过促进TNFα、IL-6、ICAM-1mRNA的表达而参与肺损伤。

Objective To investigate the role of NF-κB(nuclear factor kappa B,NF-κB) in the pathogenesis of severe acute pancreatitis-associated lung injury. Methods Sixty-six female Wistar rats were divided into normal group, SAP group and PDTC pretreated group. Pancreatitis was induced by intraductal administration of 5% sodium taurocholate. Pyrrolidine dithiocarbamate(PDTC) pretreated SAP rats was given 100 mg/kg PDTC intraperitoneally before pancreatitis was induced. Rats in SAP group, PDTC pretreated group were killed at 3,6,12 hours after induction of the model. NF-κB activity in lung tissue was detected by immunohistochemical methods. The mRNA expression of TNFα. IL-6. ICAM-1 in lung was evaluated by reverse transcription-polymerase chain reaction. We measured the ratio of wet/dry tissue as lung injury index. Results The ratio of wet/dry tissue and the levels of TNFα. IL-6. ICAM-1 mRNA increased significantly in lung tissue in SAP group comparing with normal group. The activity of NF-κB increased significantly in lung tissue from SAP group rats. PDTC decreased the ratio of wet/dry tissue, NF-kB activity in lung tissue(P<0.05) and the level of TNFα,IL-6. ICAM-1 mRNA in lung tissue (P<0.05). Conclusions There exits lung injury associated with SAP. NF-κB play damage role in severe acute pancreatitis-associated lung injury by promoting TNFα, IL-6, ICAM-1 mRNA expression. The result demonstrates that inhibition of NF-κB activity may be a promising strategy in the treatment of SAP.