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Research of Immune Response viaToll-like Receptors and Infection Control in Severe Acute Pancreatitis

重症急性胰腺炎Toll样受体免疫反应及感染控制研究

基本信息

批准号：
18591515
负责人：
SHINZEKI Makoto
金额：
$ 2万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

1. Expression of toll-like receptors (TLR), immune response via TLR, and role of TLR in severe acute pancreatitis (SAP)1) On alveolar macrophages from rats with SAP, expressions of TLR2 and TLR4 (mRNA and protein) were significantly decreased, and cytokine production was also significantly diminished.2) In intestinal mucosa in rats with SAP, TLR2 and TLR4 were expressed at the top of villi and crypt (especially at Paneth cells). The expressions of TLR2 and TLR4 proteins and NFκB activation were increased in the early phase and decreased in the late phase.3) The TLR4-deficient mice had significantly lower serum levels of AST, ALT, BUN, and creatinine; significantly lower serum levels of IL-1 and TNF; reduced apoptosis of the liver and kidney; and a significantly higher rate of positive gram-negative bacterial cultures of the pancreas.2. Expression of HMGB1 and its significance in severe acute pancreatitis1) Serum HMGB1 levels were significantly increased in patients with SAP and were correlated with disease severity.2) Serum HMGB1 levels were significantly increased in experimental SAP and expression of HMGB1 was increased in major organs (pancreas, liver, kidney, lung, and small intestine) injured during SAP.3) Blockade of HMGB1 by anti-HMGB1 antibody attenuated the development of SAP and associated organ dysfunction, but worsened the bacterial translocation to pancreas.3. Blood levels of new mediators related to immune response in severe acute pancreatitis1) Serum IL-15 levels were increased significantly in severe acute pancreatitis, and they were correlated with severity scores. Serum IL-15 levels were greater in patients with organ dysfunction, patients with infection, and nonsurvivors.2) Serum LAP levels were elevated in patients with SAP but were significantly lower in patients with higher grade of severity or pancreatic necrosis.

1. toll样受体（TLR）的表达、TLR介导的免疫应答以及TLR在严重急性胰腺炎（SAP）中的作用1)急性胰腺炎大鼠肺泡巨噬细胞中TLR2和TLR4 （mRNA和蛋白）的表达显著降低，细胞因子的产生也显著减少。2)在SAP大鼠肠黏膜中，TLR2和TLR4在绒毛和隐窝顶部表达（尤其是Paneth细胞）。TLR2、TLR4蛋白表达和NFκB活化均呈早期升高、晚期降低的趋势。3) tlr4缺陷小鼠血清AST、ALT、BUN、肌酐水平显著降低；血清IL-1、TNF水平显著降低；减少肝、肾细胞凋亡；胰脏革兰氏阴性细菌培养阳性率显著增高。HMGB1在重症急性胰腺炎中的表达及意义1)SAP患者血清HMGB1水平显著升高，且与病情严重程度相关。2)实验性SAP患者血清HMGB1水平显著升高，在SAP损伤的主要脏器（胰腺、肝脏、肾脏、肺和小肠）中HMGB1表达升高。3)抗HMGB1抗体阻断HMGB1可减轻SAP及相关脏器功能障碍的发生，但加重细菌向胰腺的易位。1)重症急性胰腺炎患者血清IL-15水平显著升高，且与严重程度评分相关。血清IL-15水平在器官功能障碍患者、感染患者和非幸存者中较高。2) SAP患者血清LAP水平升高，而严重程度较高或胰腺坏死患者血清LAP水平明显降低。