TLR4和NF-κB及细胞因子炎症反应在急性胰腺炎发病中的作用  

Role of TLR4,NF-κB and cytokine-associated inflammation reaction in acute pancreatitis

作　　者：尹金柱[1] 于丰彦[2] 曾育辉[1] 梁秋玲[1] 潘敏[1] 陈瑞芳[1] 蔡洁毅[1] 袁瑜[1] 邝小枫[1] 周季英[1] 郑超伟[3] 程明[3] 

机构地区：[1]广东药学院附属第一医院,广州510080 [2]南方医科大学珠江医院ICU,广州510282 [3]广州中医药大学第一附属医院,广州510405

出　　处：《广东医学》2011年第2期178-181,共4页Guangdong Medical Journal

基　　金：广东省医学科学技术研究基金项目(编号:WSTJJ20080108320106196803022031)

摘　　要：目的研究在急性胰腺炎发病过程中较全面反映出Toll样受体4(TLR4)通过激活NF-κB引起大量炎性递质的释放及其临床意义。方法通过应用凝胶迁移率改变分析法检测轻症和重症急性胰腺炎发病1、3、7d外周血中性粒细胞NF-κB的表达情况及应用免疫荧光流式细胞技术检测外周血单核细胞TLR4的表达,并同时检测血TNF-α、IL-1β、IL-6,分析各组数据的相关性。结果入院第1天,MAP组、SAP组TLR4表达及NF-κB活化水平显著升高且明显高于对照组,SAP组TLR4表达较MAP组更为增高,随时间延长而逐渐下降。通过Pearson相关分析表明SAP组、MAP组患者发病第1、3、7天外周血PMN内NF-κB蛋白活性及PBMCs表面TLR4的表达与APACHE-Ⅱ评分及TNF-α、IL-1β水平的变化一致,呈正相关,并随时间相关性呈递减趋势。与IL-6变化无相关性。结论在人体急性胰腺炎发病、病情进展中较全面动态地反应出TLR4通过激活NF-κB,引起大量炎性递质的释放,加重病情的进展,为今后预测疾病进展及防治提供依据。Objective To study cascade release of inflammation mediators with activation of NF-κB by TLR4 and its clinical significance in acute pancreatitis.Methods Expression of NF-κB in peripheral neutropils and TLR4 in peripheral monocytes was evaluated at 24th,72nd and 168th h in MAP and SAP using electrophoresis mobility shift assay and flow cytometry,respectively.Meanwhile,blood TNF-α,IL-1β and IL-6 were assessed.Correlation analysis was performed among groups.Results The expression of TLR4 and activation level of NF-κB were significantly increased in MAP and SAP groups,compared with those in control groups at 24th h,with more prominent increase of TLR4 expression in SAP group.These elevations descended gradually with the prolongation of time.It was revealed that the activation of NF-κB in PMN and the expression of TLR4 on PBMCs were significantly positively correlated with APACHE-Ⅱ scores and levels of TNF-α and IL-1β,and descended following a time-depend manner,during the first week in both SAP and MAP groups according to Pearson correlative analysis.However,no significant correlation with IL-6 was revealed.Conclusion The research dynamically and comprehensively shows that TLR4 causes profuse release of inflammation mediators by activating NF-κB in pathogenesis of human acute pancreatitis,which will exacerbate the condition,thus provides evidence for prognosis predicting,prevention and treatment of acute pancreatitis in the future.

关 键 词：核因子-ΚB TOLL样受体4 急性胰腺炎 

分 类 号：R657.51[医药卫生—外科学]