Endogenous and exogenous ghrelin enhance the colonic and gastric manifestations of dextran sodium sulphate-induced colitis in mice
Endogenous and exogenous ghrelin enhance the colonic and gastric manifestations of dextran sodium sulphate-induced colitis in mice
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DOI：
10.1111/j.1365-2982.2008.01184.x
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发表时间：
2009-01-01
影响因子：
3.5
通讯作者：
Depoortere, I.
中科院分区：
文献类型：
--
作者：
De Smet, B.;Thijs, T.;Depoortere, I.
胃饥饿素是一种重要的供氧肽，不仅具有促胃动力作用，而且具有免疫调节作用。本研究旨在评估内源性和外源性胃饥饿素在结肠炎发病机制中的作用，以及在这一过程中胃排空和结肠收缩功能的紊乱。在(i)胃饥饿素（+/+）和胃饥饿素（-/-）小鼠中诱导5天的右旋糖酐硫酸钠结肠炎，并在第5、10和26天监测临床和组织学参数；（ii）在海军医学研究所非近亲瑞士（NMRI）小鼠中，每天两次给予胃饥饿素（100 nmol kg(-1)）治疗，持续5或10天。用结肠平滑肌条测定神经收缩性变化，用C-14辛酸呼吸试验测定胃排空。炎症增加胃饥饿素血浆水平。胃饥饿素（-/-）小鼠的体重减轻、组织损伤、髓过氧化物酶活性和IL-1 β水平均降低。虽然缺乏胃饥饿素不影响结肠收缩性的变化，但胃饥饿素（+/+）小鼠急性期胃排空加速，而胃饥饿素（-/-）小鼠则没有。与ghrelin敲除小鼠的研究一致，外源性ghrelin治疗NMRI小鼠10天，增强了临床疾病活动性，促进了中性粒细胞的浸润和结肠IL-1 β水平。出乎意料的是，胃饥饿素治疗降低了健康而非炎症NMRI小鼠结肠的兴奋性和抑制性神经反应。内源性胃饥饿素增强炎症过程，并参与与结肠炎相关的胃排空紊乱。使用外源性胃饥饿素治疗会加重结肠炎，从而限制了胃饥饿素在肠道炎症中的潜在治疗特性。
Ghrelin is an important orexigenic peptide that not only exerts gastroprokinetic but also immunoregulatory effects. This study aimed to assess the role of endogenous and exogenous ghrelin in the pathogenesis of colitis and in the disturbances of gastric emptying and colonic contractility during this process. Dextran sodium sulphate colitis was induced for 5 days in (i) ghrelin(+/+) and ghrelin(-/-) mice and clinical and histological parameters were monitored at days 5, 10 and 26 and (ii) in Naval Medical Research Institute non-inbred Swiss (NMRI) mice treated with ghrelin (100 nmol kg(-1)) twice daily for 5 or 10 days. Neural contractility changes were measured in colonic smooth muscle strips, whereas gastric emptying was measured with the C-14 octanoic acid breath test. Inflammation increased ghrelin plasma levels. Body weight loss, histological damage, myeloperoxidase activity and IL-1 beta levels were attenuated in ghrelin(-/-) mice. Whereas absence of ghrelin did not affect changes in colonic contractility, gastric emptying in the acute phase was accelerated in ghrelin(+/+) but not in ghrelin(-/-) mice. In agreement with the studies in ghrelin knockout mice, 10 days treatment of NMRI mice with exogenous ghrelin enhanced the clinical disease activity and promoted infiltration of neutrophils and colonic IL-1 beta levels. Unexpectedly, ghrelin treatment decreased excitatory and inhibitory neural responses in the colon of healthy but not of inflamed NMRI mice. Endogenous ghrelin enhances the course of the inflammatory process and is involved in the disturbances of gastric emptying associated with colitis. Treatment with exogenous ghrelin aggravates colitis, thereby limiting the potential therapeutic properties of ghrelin during intestinal inflammation.