FFA-FABP1-PPARα轴在高脂血症性胰腺炎动物模型中促进炎症重症化演变及调控的分子机制研究

项目名称： FFA-FABP1-PPARα轴在高脂血症性胰腺炎动物模型中促进炎症重症化演变及调控的分子机制研究

项目编号： No.81200320

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 赵严

作者单位： 同济大学

项目金额： 23万元

中文摘要： 高脂血症性胰腺炎具有显著的重症和复发趋势，游离脂肪酸升高是该病的启动因素，其发病机制不详。新近研究表明，FABP1/PPARα参与了游离脂肪酸相关的代谢性疾病损伤。课题组前期采用RT-PCR显示，动物模型中高脂血症性胰腺炎及正常胰腺组织中均有FABP1表达，qRT-PCR提示在高脂血症性胰腺炎组FABP1明显高表达，而PPARα表达减弱，且胰腺腺泡损伤更严重，故推测FFA/FABP1/PPARα可能参与了高脂血症性胰腺炎的进展。目前需要解决的难题是FFA/FABPs/PPARs如何导致高脂血症性胰腺炎重症化。本研究采用体内外高脂血症性胰腺炎模型，探讨FFA/FABP1/PPARα轴促进高脂血症性胰腺炎腺泡细胞坏死与严重重症化演变的作用及其调控机制，并以免疫共沉淀法研究PPARα相互作用的蛋白或下游靶蛋白，以期拓展高脂血症性胰腺炎发病机制。

中文关键词： 高脂血症性胰腺炎；脂肪酸结合蛋白；过氧化物酶体增殖物激活受体；；

英文摘要： Hyperlipidemic pancreatitis with severe and recurrent trends, free fatty acids increased start-up factors of the disease, its pathogenesis is unknown. Recent studies indicated that liver-type fatty acid binding protein(L-FABP) or Peroxisome proliferator activated receptor(PPAR) is involved in Free fat acid ( FFA ) related to metabolic disease damage. Previous studies have chosen PT-PCR for indicate that the expression of FABP1 were detected in both the group of hyperlipidemic pancreatitis model and normal pancreatic tissues; however FABP1 is over-expression in hyperlipidemic pancreatic tissue by qRT-pcr, PPAR Alpha is weakened and pancreatic acinar is damaged more seriously. It is speculated that the FFA/FABP1/PPARα may be involved in the progress of hyperlipidemic pancreatitis. But, how the FFA/PPARs/FABPs resulted in development of hyperlipidemic pancreatitis is an unsolved problem. In this study, in vitro and in vivo hyperlipidemic pancreatitis model, to detect the regulatory mechanism about FFA/ FABP1 /PPARα axis promoting pancreatic acini necrosis in hyperlipidemic severe acute pancreatitis， and co-immunoprecipitationmethod PPARα interacting proteins or downstream target proteins in order to expand the pathogenesis of hyperlipidemic pancreatitis.

英文关键词： hyperlipidemic acute pancreatitis；fatty acid binding protein；peroxisome proliferator-activated receptor；；