蛋白酶激活受体2参与慢性胰腺炎疼痛形成的机制研究

项目名称： 蛋白酶激活受体2参与慢性胰腺炎疼痛形成的机制研究

项目编号： No.30871157

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 李兆申

作者单位： 中国人民解放军第二军医大学

项目金额： 32万元

中文摘要： 背景：慢性胰腺炎（CP）发病率逐年升高，其引起疼痛的机制尚不清楚。目标：蛋白酶激活受体2（PAR2）、辣椒素（TRPV1 ）受体在CP模型导致大鼠疼痛发病机制中的作用。方法：采用胰胆管内逆行注射 TNBS的方法建立CP大鼠模型；采用热撤回反应评估大鼠腹部痛觉过敏，通过免疫荧光和免疫蛋白印迹法评估PAR2和TRPV1的表达变化。并评估大剂量萘普生对CP大鼠热痛觉阈值及对胰腺组织纤维化的影响。结果：CP大鼠腹部热痛阈值下降，在DRGs中PAR2和TRPV1的表达显著上调，且PAR2的表达和腹部热痛阈及TRPV1的表达高度相关。大剂量萘普生降低CP大鼠腹部热痛阈，并加重了胰腺损伤及纤维化。结论：CP大鼠热痛觉过敏和DRGs中PAR2表达上调相关，大剂量萘普生可以加重胰腺损伤及纤维化。

中文关键词： 慢性胰腺炎；疼痛；蛋白酶激活受体2；纤维化

英文摘要： Background：The incidence of chronic pancreatitis (CP) was significantly increased，but the mechanism of pain caused by CP is not clear. Aims: The roles of protease activated receptor2 (PAR 2) and transient receptor potential vanilloid 1 (TRPV1) receptors in the pathogenesis of pain in CP models. Methods: CP model was induced by trinitrobenzene sulfonic acid infusion (TNBS) into rat pancreatic ducts. Abdominal hyperalgesia was measured by thermal withdrawal latencies. The expression of PAR2 and TRPV1 were analyzed by immunofluorescence and Western blot. The effects of high-dose naproxen administered orally on abdominal thermal hyperalgesia and pancreas of rats with CP were measured. Results: Rats with CP showed a decreased thermal withdrawal latency. PAR2 and TRPV1 were significantly upregulated in DRGs. The increased PAR2 protein expression was tightly correlated with thermal withdrawal latencies and TRPV1 expression. High-dose naproxen treatment decreased the thermal thresholds of CP rats and aggravated pancreatic damage and fibrosis. Conclusions: The thermal hyperalgesia in CP is associated with an up-regulation of the PAR2 in DRGs. High-dose naproxen treatment aggravated pancreatic fibrosis.

英文关键词： chronic pancreatitis;pain;PAR2;fibrosis