CMGH：新型信号分子的发现或可帮助开发治疗胰腺炎的创新性疗法

  最近，发表在国际杂志Cellular and Molecular Gastroenterology and Hepatology上的一篇研究论文中，来自杜克大学的研究人员通过研究发现，由产生胰腺消化酶的腺泡细胞产生的信号对于胰腺炎患者疼痛和炎症的发生非常关键。研究者表示，包括胰腺腺泡细胞、神经细胞及免疫细胞在内产生的细胞间信号网络会引发胰腺炎的进展，但白三烯B4可以通过腺泡细胞合成并释放，随后激活感觉神经来诱发急性胰腺炎患者机体疼痛及炎性发生。如果研究人员可以开发出阻断白三烯B4的疗法，就可以有效缓解患者机体的疼痛和炎症的发生了。
  文章中，研究人员利用小鼠模型进行研究，此前研究发现感觉神经上的瞬时受体电位香草酸亚型1（TRPV1）受体主要参与胰腺炎患者机体的疼痛和炎症过程，而TRPV1受体的激活在胰腺炎早期发生阶段也扮演着重要角色，因此研究人员就想去研究这些受体是如何被激活的，结果就发现白三烯B4在该过程发挥着重要作用。
  研究结果表明，通过抑制5-脂氧合酶来靶向作用白三烯B4对于实验性的慢性胰腺炎是非常有益的，5-脂氧合酶是对白三烯B4合成非常关键的一种酶类，相关研究或可帮助研究人员针对胰腺炎病人开发5-脂氧合酶的抑制剂并且对其进行评估。
  研究者Jerrold Turner说道，本文研究或可帮助开发治疗胰腺炎的新策略，胰腺癌是一种和很多疾病相伴催在的复杂疾病，比如囊性纤维化和酒精中毒等；当前疗法较少以及针对炎症相关的疼痛的管理措施是当前治疗胰腺炎的主要障碍，患者经常会需要麻醉品来进行治疗，但麻醉品的使用非常危险，而且往往会增加胰腺炎患者其它的问题。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Acinar Cell Production of Leukotriene B4 Contributes to Development of Neurogenic Pancreatitis in Mice 
CMGH Cellular and Molecular Gastroenterology and Hepatology         doi:10.1016/j.jcmgh.2014.11.002
Rafiq A. Shahid1, Steven R. Vigna1, 2, Amanda C. Layne3, Joelle M.-J. Romac1, Rodger A. Liddle1, 4
Background & Aims
In the pancreas, activation of primary sensory nerves through the transient receptor potential vanilloid-1 (TRPV1) ion channel contributes to the early stages of development of pancreatitis. Little is known about the mechanism by which this occurs. We investigated whether leukotriene B4 (LTB4) is an endogenous agonist of TRPV1 and mediates pancreatitis.
Methods
Acute inflammation was induced in the pancreata of Trpv1−/− mice and their wild-type littermates by retrograde infusion of the main pancreatic duct with 2% sodium taurocholate (NaT) or intraperitoneal injections of caerulein. Mice were also given injections of resiniferatoxin (an excitotoxin that desensitizes TRPV1) or MK886 (a drug that inhibits LTB4 biosynthesis). Pancreatic tissues and plasma were collected and analyzed.
Results
Retrograde perfusion of the main pancreatic ducts of wild-type mice with NaT caused severe acute pancreatitis; the severity was reduced by coadministration of resiniferatoxin. Trpv1−/− mice developed a less severe pancreatitis after NaT administration compared with controls. Administration of MK886 before perfusion with NaT also significantly reduced the severity of pancreatitis in wild-type mice. Pancreatic tissues from mice given NaT had a marked increase in the level of 5-lipoxygenase immunoreactivity specifically in acinar cells. Bile acid and caerulein induced secretion of LTB4 by cultured pancreatic acinar cells; MK886 inhibited this process.
Conclusions
Administration of caerulein or intraductal bile acids in mice causes production of LTB4 by pancreatic acinar cells. This activates TRPV1 on primary sensory nerves to induce acute pancreatitis.