中性白细胞活动对胰腺腺泡细胞钙离子信号的调节

项目名称： 中性白细胞活动对胰腺腺泡细胞钙离子信号的调节

项目编号： No.31270892

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 崔宗杰

作者单位： 北京师范大学

项目金额： 80万元

中文摘要： 急性胰腺炎早期的白细胞侵润，已经经过多年的系统研究并被确认。但是中性白细胞侵润在急性胰腺炎发生发展中的细胞和分子基础，并不清楚。本项目计划分离大鼠中性白细胞，将分离提纯的白细胞与分离的大鼠胰腺腺泡共孵育。研究生理性刺激物触发中性白细胞呼吸爆发、产生胞外陷阱的特性。研究中性白细胞呼吸爆发、胞外陷阱形成，对分离胰腺腺泡细胞中G蛋白偶联受体CCK1、M3所引发胞浆钙振荡的调节作用。鉴别白细胞呼吸爆发、胞外陷阱的成份，对两种G蛋白偶联受体功能的影响。作为对照，同时将研究中性白细胞两种生理过程（呼吸爆发、胞外陷阱）对肝脏实质细胞表面alpha 1型肾上腺素能受体、V1A型血管加压素受体、P2Y型嘌呤能受体的调节作用。这项研究对于从分子水平阐明中性白细胞侵润在急性胰腺炎发生发展中的作用，具有重要意义。潜在地可对急性胰腺炎的早期预防及治疗，起到一定的指导作用。

中文关键词： 中性粒细胞；胰腺腺泡细胞；胞浆钙振荡；CCK1型受体；呼吸爆发

英文摘要： Neutrophil infiltration during the initial phase of acute pancretitis is a well established fact. But the physiological or pathophysiological significance is not well elucidated at the cellular or molecular level. In the present project, freshly isolated rat neutrophils will be co-incubated with freshly isolated rat pancreatic acini. Both respiratory burst and extracellular traps will be induced by physiolgical stimuli of the neutrophils. Both processes will be characterized in vitro. The effects of both respiratory burst and extracellular trap formation on cytosolic calcium oscillations induced by the G-protein coupled receptors CCK1 and M3 receptors will be examined. Isolated rat hepatocytes will be used as control cells to investigate neutrophil effects on alpha1 adrenergic, V1A vasopressin, and P2Y purinergic receptors. Effects of individual components of respiratory burst and extraccelular traps on pancreatic acinar cell calcium signalling will be examined. This project tries to elucidate at the molecular level the role for neutrophils in the initiation and progression of acute pancreatitis. This may have important implications in the prevention and possibly treatment of acute pancreatitis, especially of severe acute pancreatitis.

英文关键词： neutrophils；pancreatic acinar cells；cytosolic calcium oscillations；CCK1 receptors；respiratory burst