胃饥饿素在小鼠结肠炎模型中的治疗作用。

Therapeutic action of ghrelin in a mouse model of colitis.

作者信息

Gonzalez-Rey Elena, Chorny Alejo, Delgado Mario

机构信息

Institute of Parasitology and Biomedicine, CSIC, Granada, Spain.

出版信息

Gastroenterology. 2006 May;130(6):1707-20. doi: 10.1053/j.gastro.2006.01.041.

DOI:10.1053/j.gastro.2006.01.041

PMID:16697735

Abstract

BACKGROUND & AIMS: Ghrelin is a novel growth hormone-releasing peptide with potential endogenous anti-inflammatory activities ameliorating some pathologic inflammatory conditions. Crohn's disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon. The aim of this study was to investigate the therapeutic effect of ghrelin in a murine model of colitis.

METHODS

We examined the anti-inflammatory action of ghrelin in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid. Diverse clinical signs of the disease were evaluated, including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of ghrelin, such as inflammatory cytokines and chemokines, Th1-type response, and regulatory factors.

RESULTS

Ghrelin ameliorated significantly the clinical and histopathologic severity of the trinitrobenzene sulfonic acid-induced colitis; abrogating body weight loss, diarrhea, and inflammation; and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response through the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of interluekin-10/transforming growth factor-beta1-secreting regulatory T cells in this therapeutic effect was demonstrated. Importantly, the ghrelin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease.

CONCLUSIONS

Our data demonstrate novel anti-inflammatory actions for ghrelin in the gastrointestinal tract, ie, the capacity to deactivate the intestinal inflammatory response and to restore mucosal immune tolerance at multiple levels. Consequently, ghrelin administration represents a novel possible therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis.

摘要

背景与目的

胃饥饿素是一种新型的生长激素释放肽，具有潜在的内源性抗炎活性，可改善某些病理性炎症状态。克罗恩病是一种慢性衰弱性疾病，其特征为结肠严重的辅助性T细胞1（Th1）驱动的炎症。本研究的目的是探讨胃饥饿素在小鼠结肠炎模型中的治疗效果。

方法

我们检测了胃饥饿素在经结肠内注射三硝基苯磺酸诱导的结肠炎中的抗炎作用。评估了该疾病的多种临床症状，包括体重减轻、腹泻、结肠炎和组织病理学变化。我们还研究了胃饥饿素潜在治疗作用所涉及的机制，如炎性细胞因子和趋化因子、Th1型反应以及调节因子。

结果

胃饥饿素显著改善了三硝基苯磺酸诱导的结肠炎的临床和组织病理学严重程度；消除了体重减轻、腹泻和炎症；并提高了生存率。这种治疗效果与通过调节多种炎性介质下调炎症和Th1驱动的自身免疫反应有关。此外，还证明了分泌白细胞介素-10/转化生长因子-β1的调节性T细胞部分参与了这种治疗效果。重要的是，胃饥饿素治疗对已确诊的结肠炎具有治疗效果，并避免了疾病的复发。