胆汁酸对胰腺腺泡细胞内miR-155表达的影响及其机制研究

项目名称： 胆汁酸对胰腺腺泡细胞内miR-155表达的影响及其机制研究

项目编号： No.81500484

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李之拓

作者单位： 哈尔滨医科大学

项目金额： 17万元

中文摘要： 重症急性胰腺炎诱发全身炎症反应综合征的机制尚未完全阐明。Toll样受体可通过识别机体内源性物质及信号传导引发炎症反应或对该反应进行调控。miR-155是一种新发现的TLR信号通路的调控因子，其表达受PI3K/AKT信号通路的调节，但胆汁酸能否激活胰腺腺泡细胞内PI3K/AKT信号通路尚未见报道。我们的前期实验发现，胆汁酸作用于大鼠胰腺腺泡AR42J细胞20分钟，既可在细胞内检测到TLR信号通路的多个信号分子表达水平明显升高。我们假设，胆汁酸通过PI3K/AKT信号通路抑制miR-155的表达促使TLR信号通路的激活。为验证这一假说，我们利用AR42J细胞和大鼠建立胰腺炎模型，采用RT-PCR、腺病毒载体转染等手段，从细胞及组织等多方面探讨miR-155对重症胰腺炎炎症反应的调控作用，明确胆汁酸调节miR-155表达的机制。以期发现调控胆源性胰腺炎时炎症反应的新靶点，为胰腺炎的治疗提供新方法

中文关键词： 急性胰腺炎；全身炎症反应综合征；信号通路

英文摘要： Severe acute pancreatitis (SAP) is a clinically severe disease, the most serious complication of which is systemic inflammatory response syndrome (SIRS); its mechanism is not fully understood. Toll-like receptors (TLRs) can cause inflammation or regulate the reaction by identifying endogenous substances and signal transduction. miR-155 is a newly discovered regulator of TLR signaling pathway, and its expression is regulated by PI3K/AKT signaling pathway, but it has not been reported that whether bile acids can activate the PI3K/AKT signaling pathway in pancreatic acinar cells. In our previous study, we found that trypsinogen activation can be detected in rat AR42J pancreatic acinar cells in 20 minutes after treated with bile acids (taurolithocholic acid 3-sulfate, TLC-S); meanwhile, the expression levels of multiple signal molecules in TLR signaling pathway were significantly increased. In view of the close relationship between miR-155 and TLR pathway, we hypothesize that bile acids can prompt the activation of TLR signaling pathway by PI3K/AKT signaling pathway mediated inhibition of miR-155. To test this hypothesis, we will establish severe pancreatitis model using pancreatic acinar AR42J cells and rat, employing techniques, such as real time PCR, Western blot, adenovirus vector transfection, to explore the role of miR-155 on the regulation of inflammation in severe pancreatitis and identify that bile acids can regulate the expression of miR-155 by PI3K/AKT signaling pathway. This study will provide a new target that can regulate inflammatory response in biliary acute pancreatitis and provide a new method for the treatment of pancreatitis.

英文关键词： Acute pancreatitis;Systemic inflammatory response;Signaling pathway