Acute and chronic responses associated with adrenomedullin administration in experimental colitis
Acute and chronic responses associated with adrenomedullin administration in experimental colitis
复制标题
DOI：
10.1016/j.peptides.2008.07.013
复制
发表时间：
2008-11-01
期刊：
影响因子：
3
通讯作者：
Motilva, V.
中科院分区：
文献类型：
--
作者：
Talero, E.;Sanchez-Fidalgo, S.;Motilva, V.
肾上腺髓质素（AM）是一种由52个氨基酸组成的多肽，属于降钙素基因相关肽（CGRP）超家族成员。鉴于AM在各种实验模型中已成为潜在的免疫调节剂和抗炎剂，本研究已深入到其在肠道炎症中的可能治疗作用，分析了TNBS诱导的大鼠结肠炎的急性和慢性（14和21天）阶段的反应。在急性模型中，AM处理降低了腹泻的发生率和结肠损伤的严重程度，并在三个测定剂量（50、100和200 ng/kg动物）下提高了存活率。AM给药能够减少TNF-α的早期产生，并协同维持IFN-γ和IL-10的基础水平。在慢性研究中，肽减弱了损伤的程度，体重减轻和腹泻的发生率较低（50和100 ng/kg动物）。细胞中性粒细胞浸润，随后增加髓过氧化物酶（MPO）水平引起的TNBS，减少慢性AM管理后。该肽在Thl/Th 2细胞因子平衡和慢性疾病恢复的演变中发挥作用：促炎性TNF-α和IFN-γ的水平降低，抗炎性IL-10显著增加。环氧合酶-2（考克斯-2）和一氧化氮合酶（iNOS）的蛋白表达没有修改AM管理，虽然减少一氧化氮（NO）的生产可以检测到在慢性模型。这些结果支持AM作为抗炎因子的作用，在肠道炎症性结肠炎中具有有益作用。(C)2008年爱思唯尔公司All rights reserved.
Adrenomedullin (AM) is a 52 amino acid peptide and member of the calcitonin gene-related peptide (CGRP) super family. Given that AM has emerged as a potential immuno-regulatory and anti-inflammatory agent in various experimental models, this study has deepened into its possible therapeutic effect in intestinal inflammation analyzing the responses in both acute and chronic (14 and 21 days) phases of TNBS-induced colitis in rats. In the acute model, AM treatment reduced the incidence of diarrhea and the severity of colonic damage, and improved the survival rate at the three doses assayed (50, 100, and 200 ng/kg animal). AM administration was able to reduce the early production of TNF-alpha and collaborated to maintaining basal levels of IFN-gamma and IL-10. In the chronic studies the peptide attenuated the extent of the damage with lesser incidence of weight loss and diarrhea (SO and 100 ng/kg animal). Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase (MPO) levels caused by TNBS, was reduced after chronic AM administration. The peptide played a role in the evolution of Thl/Th2 cytokines balance and chronic disease recuperation: levels of proinflammatory TNF-alpha and IFN-gamma decreased and anti-inflammatory IL-10 increased significantly. Cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) protein expression were not modified by AM administration, although a reduction of nitric oxide (NO) production could be detected in the chronic model. These results support a role of AM as an anti-inflammatory factor with beneficial effects in intestinal inflammatory colitis. (C) 2008 Elsevier Inc. All rights reserved.