Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Pancreatology. 2009;9(5):662-9. doi: 10.1159/000212099. Epub 2009 Aug 14.
Microcirculatory disturbances are known to play a pivotal role in the pathogenesis of severe necrotizing pancreatitis (SNP). Calcitonin gene-related peptide (CGRP) is a vasodilatatory neuropeptide with potential anti-inflammatory effects. This study characterizes the protective effects and the anti-inflammatory pathway of exogenous CGRP in SNP.
SNP was induced in rats using the glycodeoxycholic acid model. CGRP was injected prophylactically before or therapeutically after initiation of the disease. Pancreatic damage was assessed using intravital microscopy, histology, NF-kappaB p50/p65 electrophoretic mobility shift assay, serum cytokine assay and ICAM-1 immunohistochemistry at 6 or 12 h after the onset of disease.
Pancreatic microcirculatory disturbances, nuclear NF-kappaB levels and pancreatic ICAM-1 expression were increased in SNP compared to controls. After CGRP application, microcirculatory disturbances, NF-kappaB levels and pancreatic ICAM-1 expression were attenuated compared to pancreatitis alone. Moreover, pancreatic morphologic damage was significantly reduced by both prophylactic and therapeutic application of CGRP.
CGRP is a neuropeptide that ameliorates the development of SNP in rats and may provide new treatment options. Its anti-inflammatory effects appear to be mediated by the modulation of pancreatic microcirculation and the inflammatory cascade.
微循环障碍在重症坏死性胰腺炎（SNP）的发病机制中起着关键作用。降钙素基因相关肽（CGRP）是一种具有潜在抗炎作用的血管扩张神经肽。本研究旨在探讨外源性 CGRP 在 SNP 中的保护作用及其抗炎途径。
采用甘氨脱氧胆酸模型诱导大鼠 SNP。在疾病发作前预防性或治疗性注射 CGRP。疾病发作后 6 或 12 小时，通过活体显微镜、组织学、NF-κB p50/p65 电泳迁移率变动分析、血清细胞因子测定和 ICAM-1 免疫组化评估胰腺损伤。
与对照组相比，SNP 大鼠的胰腺微循环障碍、核 NF-κB 水平和胰腺 ICAM-1 表达增加。与胰腺炎组相比，CGRP 应用后，微循环障碍、NF-κB 水平和胰腺 ICAM-1 表达减弱。此外，预防性和治疗性应用 CGRP 均可显著减轻胰腺形态学损伤。
CGRP 是一种神经肽，可改善 SNP 大鼠的发展，可能为治疗提供新的选择。其抗炎作用可能通过调节胰腺微循环和炎症级联反应来实现。
