Department of Pharmacology, School of Pharmacy, University of Seville, 41012 Seville, Spain.
Mediators Inflamm. 2012;2012:717851. doi: 10.1155/2012/717851. Epub 2012 May 20.
Adrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by injection of CAR into the pleural cavity of mice. AM (200 ng/kg) was administered by intraperitoneal route 1 h after CAR, and the animals were sacrificed 4 h after that. AM treatment attenuated the recruitment of leucocytes in the lung tissue and the generation and/or the expression of the proinflammatory cytokines as well as the expression of the intercellular cell adhesion molecules. Moreover, AM inhibited the induction of inducible nitric oxide synthase (iNOS), thereby abating the generation of nitric oxide (NO) and prevented the oxidative and nitroxidative lung tissue injury, as shown by the reduction of nitrotyrosine, malondialdehyde (MDA), and poly (ADP-ribose) polymerase (PARP) levels. Finally, we demonstrated that these anti-inflammatory effects of AM were associated with the inhibition of nuclear factor-κB (NF-κB) activation. All these parameters were markedly increased by intrapleural CAR in the absence of any treatment. We report that treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors.
肾上腺髓质素 (AM) 是一种含有 52 个氨基酸的肽，具有显著的抗炎活性。在本研究中，我们评估了该肽在角叉菜胶（CAR）诱导的胸膜炎实验性炎症模型中的潜在治疗效果。通过向小鼠胸膜腔注射 CAR 诱导胸膜炎。在 CAR 后 1 小时通过腹腔内途径给予 AM（200 ng/kg），并在那之后 4 小时处死动物。AM 治疗减轻了肺组织中白细胞的募集以及促炎细胞因子的生成和/或表达以及细胞间黏附分子的表达。此外，AM 抑制诱导型一氧化氮合酶（iNOS）的诱导，从而减少一氧化氮（NO）的生成，并防止氧化和硝化肺组织损伤，如硝基酪氨酸、丙二醛（MDA）和多（ADP-核糖）聚合酶（PARP）水平的降低所示。最后，我们证明 AM 的这些抗炎作用与核因子-κB（NF-κB）激活的抑制有关。在没有任何治疗的情况下，胸腔内 CAR 明显增加了所有这些参数。我们报告说，AM 的治疗通过下调广泛的炎症因子显著减少了急性肺损伤的发展。
