IRF-2调控SNAREs蛋白介导的自噬参与急性胰腺炎发生的机制研究

At present some research showed that trypsinogen activation in pancreatic acinar cells is an early original initiating factor of acute pancreatitis. autophagy mechanism get involved in the prossess, but the exact mechanism has not been elucidated. Recently the effect of transcription factor IRF-2 in acute pancreatitis induced researchers' attention. In our previous study we found that autophagy in the acute pancreatitis rat pancreatic cells increased significantly, and IRF-2 is highly expressed. But there are no reports whether IRF-2 can affect acute pancreatitis through the regulation of autophagy currently. Therefore, this project intends to do some observations about the decisive role of autophagy, IRF-2 and the higher number of SNAREs protein family in the development of acute pancreatitis through in vitro and in vivo experiments. Then, we upward or interference the IRF-2 gene to explore whether IRF-2 can affect the the acute pancreatitis process through regulation of autophagy. At the end, we do some preliminary study on the role of SNAREs protein and iNOS/NO signaling pathway. The purpose of this study was to confirm our hypothesis: IRF-2 gene can mediate autophagy mechanism through the regulation of SNAREs complex to affect the.development of the acute pancreatitis process, and the effection is closely related to the role of iNOS/NO signaling pathway. As a result, we can change the disease process of acute pancreatitis through the intervention of autophagy and related signaling pathways. This study will help to reveal the molecular mechanisms involved in the autophagy mechanism and the process of acute pancreatitis and to provide a theoretical basis for exploring the prevention and treatment of acute pancreatitis.

胰腺腺泡细胞内胰蛋白酶原提前激活是急性胰腺炎（AP）的启动因素，自噬作用参与其中，但具体机制尚未阐明。近期发现IRF-2可以调节胰腺腺泡细胞内酶原的活化与释放。我们前期研究发现AP大鼠胰腺细胞内自噬体明显增多，IRF-2异常高表达，但IRF-2是否可以通过调控自噬影响AP目前尚无相关报道。因此，本课题拟通过体内外实验观察自噬及IRF-2、SNAREs蛋白家族在AP发生发展中的决定作用；通过对IRF-2基因进行上调或干扰后，探讨IRF-2是否通过调控自噬影响AP进程；并初步研究SNAREs蛋白及iNOS/NO信号通路的作用。本研究旨在证实我们的假设：IRF-2可能通过调控SNAREs蛋白介导的自噬机制影响AP的发生发展，其作用可能与iNOS/NO信号通路密切相关，通过对自噬及相关信号通路的干预可以影响AP的疾病进程。本研究有助于揭示自噬参与AP的分子机制，为探索AP的临床防治提供理论依据。

急性胰腺炎是一种严重危害健康的急危重症，胰腺腺泡细胞内胰蛋白酶原提前激活是急性胰腺炎（AP）的启动因素，自噬作用参与其中，但具体机制尚未阐明。近期发现IRF-2可以调节胰腺腺泡细胞内酶原的活化与释放。我们前期研究发现AP大鼠胰腺细胞内自噬体明显增多，IRF-2异常高表达，但IRF-2是否可以通过调控自噬影响AP目前尚无相关报道。因此，本课题拟通过体内外实验观察自噬及IRF-2、SNAREs蛋白家族在AP发生发展中的决定作用；通过对IRF-2基因进行上调或干扰后，探讨IRF-2是否通过调控自噬影响AP进程；并初步研SNAREs蛋白及iNOS/NO信号通路的作用。本研究旨在证实我们的假设：IRF-2可能通过调控SNAREs蛋白介导的自噬机制影响AP的发生发展，其作用可能与iNOS/NO信号通路密切相关，通过对自噬及相关信号通路的干预可以影响AP的疾病进程。本研究有助于揭示自噬参与AP的分子机制，为探索AP的临床防治提供理论依据。