Intraductal administration of an NK1 receptor antagonist attenuates the inflammatory response to retrograde infusion of radiological contrast in rats: Implications for the pathogenesis and prevention of ERCP-induced pancreatitis
Intraductal administration of an NK1 receptor antagonist attenuates the inflammatory response to retrograde infusion of radiological contrast in rats: Implications for the pathogenesis and prevention of ERCP-induced pancreatitis
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DOI：
10.1097/00006676-200307000-00018
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发表时间：
2003-07-01
期刊：
影响因子：
2.9
通讯作者：
Pasricha, PJ
中科院分区：
文献类型：
--
作者：
He, ZJ;Winston, JH;Pasricha, PJ
神经源性炎症介质P物质（SP）参与了促分泌素诱导的急性胰腺炎的发病机制。我们推测，它也可能在内镜逆行胰胆管造影（ERCP）后急性胰腺炎的发展中发挥重要作用。目的：我们的目的是评价CP-96345（一种NK 1受体拮抗剂）在大鼠模型中减少ERCP术后胰腺炎的有效性。研究方法：在逆行造影剂输注引起的胰腺炎大鼠模型中研究了CP-96345与造影剂混合时的作用。24小时后，评价胰腺组织学、水肿和髓过氧化物酶活性（MPO）、血浆淀粉酶和胰腺腺泡细胞中NK 1受体内吞作用。结果如下：导管内造影剂灌注引起血浆淀粉酶、水肿、组织学分级和胰腺MPO以及胰腺腺泡细胞中NK 1受体内化的增加。在输注液中加入CP-96345可显著降低胰腺水肿、MPO活性和胰腺炎的组织学分级，并伴有NK 1受体内化的降低。结论：当NK 1受体拮抗剂与造影剂一起沿着递送时，由导管内造影剂输注引起的胰腺炎症显著减少。这些结果提供了一些深入了解ERCP诱发胰腺炎的发病机制，以及目前的新的药理学靶点，其预防。
The neurogenic inflammatory mediator, substance P (SP), has been implicated in the pathogenesis of acute secretagogue-induced pancreatitis. We hypothesized that it may also play an important role in the development of acute pancreatitis after endoscopic retrograde cholangiopancreatography ( ERCP). Aims: Our aim was to evaluate the effectiveness of CP-96345, a NK1 receptor antagonist, in diminishing post-ERCP pancreatitis in a rat model. Methods: The effects of CP-96345, when mixed with the contrast agent, were studied in a rat model of pancreatitis caused by retrograde contrast infusion. After 24 hours, histology, edema, and myeloperoxidase activity (MPO) of pancreas, plasma amylase, and NK1 receptor endocytosis in pancreatic acinar cells were evaluated. Results: Intraductal contrast infusion caused increases in plasma amylase, edema, histologic grade, and MPO of pancreas, and NK1 receptor internalization in pancreatic acinar cells. The addition of CP-96345 to the infusate significantly reduced pancreatic edema, MPO activity, and the histologic grade of pancreatitis accompanied by a decrease in NK1 receptor internalization. Conclusions: When an NK1 receptor antagonist is delivered along with the contrast media there is significant reduction in the pancreatic inflammation caused by intraductal contrast infusion. These results provide some insight into the pathogenesis of ERCP induced pancreatitis as well as present novel pharmacological targets for its prevention.