Yan Lu, Li Qing-Fu, Rong Yan-Ting, Chen Yong-Heng, Huang Zhao-Hong, Wang Zhi-Zhi, Peng Jie
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Oncol Lett. 2018 Mar;15(3):3121-3126. doi: 10.3892/ol.2017.7659. Epub 2017 Dec 20.
Acute pancreatitis (AP) is the acute inflammation of the pancreas. The morbidity of AP has increased in recent years. Certain patients eventually develop severe AP (SAP), which rapidly progresses to multiple organ dysfunction; the incidence of this occurring in patients with AP is 20-30%. To date, no specific drugs or methods exist to treat this disease. Rutaecarpine relaxes vascular smooth muscle by stimulating calcitonin gene-related peptide (CGRP) release via activation of vanilloid receptor subtype 1 (VR1). It has been demonstrated that rutaecarpine induces a therapeutic effect on SAP. The present study was conducted to characterize the molecular mechanisms underlying the protective effects of rutaecarpine against AP using a rat model of AP. Gross pathological changes of the pancreas, as well as the pancreatic tissue histopathological score, were assessed following treatment with rutaecarpine, capsazepine or a combination of the two. Serum amylase activity was detected using an automatic biochemistry analyzer. Changes in the serum concentrations of interleukin (IL)-6, tumor necrosis factor (TNF-α), IL-10 and CGRP were assessed by ELISA and radioimmunoassay. The results demonstrated that pre-treatment with rutaecarpine markedly decreased pancreatic inflammation and necrosis, reduced the volume of ascites, and significantly increased the plasma concentration of CGRP and the serum concentration of IL-10, an anti-inflammatory cytokine. However, serum concentrations of the inflammatory cytokines IL-6 and TNF-α were decreased. The effect of rutaecarpine treatment markedly improved with increases in the drug dose. Capsazepine, as a competitive vanilloid receptor antagonist, abolished these protective effects of rutaecarpine against AP. Therefore, the results of the present study indicate that rutaecarpine protects against AP in rats by upregulating endogenous CGRP release via activation VR1 of, to improving the microcirculation of the pancreatic tissue and regulate the expression of inflammatory factors.
急性胰腺炎（AP）是胰腺的急性炎症。近年来，AP的发病率有所上升。某些患者最终会发展为重症急性胰腺炎（SAP），并迅速进展为多器官功能障碍；AP患者中发生这种情况的发生率为20%-30%。迄今为止，尚无治疗该疾病的特效药物或方法。吴茱萸次碱通过激活香草酸受体1型（VR1）刺激降钙素基因相关肽（CGRP）释放，从而舒张血管平滑肌。已证实吴茱萸次碱对SAP具有治疗作用。本研究旨在利用AP大鼠模型，阐明吴茱萸次碱对AP保护作用的分子机制。在用吴茱萸次碱、辣椒素或两者联合处理后，评估胰腺的大体病理变化以及胰腺组织病理评分。使用自动生化分析仪检测血清淀粉酶活性。通过酶联免疫吸附测定（ELISA）和放射免疫测定评估血清白细胞介素（IL）-6、肿瘤坏死因子（TNF-α）、IL-10和CGRP浓度的变化。结果表明，预先用吴茱萸次碱处理可显著减轻胰腺炎症和坏死，减少腹水体积，并显著提高血浆CGRP浓度和抗炎细胞因子IL-10的血清浓度。然而，炎症细胞因子IL-6和TNF-α的血清浓度降低。随着药物剂量增加，吴茱萸次碱治疗效果明显改善。辣椒素作为竞争性香草酸受体拮抗剂，消除了吴茱萸次碱对AP的这些保护作用。因此，本研究结果表明，吴茱萸次碱通过激活VR1上调内源性CGRP释放，改善胰腺组织微循环并调节炎症因子表达，从而对大鼠AP起到保护作用。
