The anti-inflammatory effect of leptin on experimental colitis:: involvement of endogenous glucocorticoids
The anti-inflammatory effect of leptin on experimental colitis:: involvement of endogenous glucocorticoids
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DOI：
10.1016/j.peptides.2003.11.005
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发表时间：
2004-01-01
期刊：
影响因子：
3
通讯作者：
Yegen, BÇ
中科院分区：
文献类型：
--
作者：
Çakir, B;Bozkurt, A;Yegen, BÇ
本研究旨在比较瘦素对急性结肠炎症的影响与急性应激暴露的影响，后者通过下丘脑-垂体-肾上腺（HPA）轴发挥作用。对两种性别的 Sprague-Dawley 大鼠进行直肠内注射乙酸。在诱导结肠炎之前和之后6小时注射瘦素（10μg/kg；腹腔注射）或盐水。一组大鼠在结肠炎诱导后第 6 小时受到回避水应激 (WAS) 30 分钟。 RU-486（2 mg/kg；腹腔注射）是一种糖皮质激素受体拮抗剂，在首次瘦素注射前 12 小时和 1 小时以及第二次瘦素注射或暴露于 WAS 前 1 小时腹膜内注射。 24小时处死大鼠，切除远端8cm结肠进行宏观和微观评分，测定组织湿重指数（WI）和组织髓过氧化物酶活性（MPO）。与对照组相比，乙酸诱导的结肠炎显着增加了宏观和微观损伤评分、WI 和 MPO。暴露于急性WAS或瘦素治疗可降低结肠炎引起的损伤评分、WI和MPO的升高，但当WAS和瘦素一起应用时，没有观察到附加抑制作用。 RU-486 治疗逆转了瘦素或 WAS 对结肠炎症的抑制作用。我们的结果表明，外源性瘦素模拟了 HPA 轴激活对结肠炎诱导的炎症过程的影响。结果还表明，瘦素的抗炎作用涉及组织中性粒细胞依赖性机制，并且依赖于糖皮质激素的释放。 (C) 2003 Elsevier Inc. 保留所有权利。
The present study was designed to compare the effect of leptin on acute colonic inflammation with that of acute stress exposure, which acts via the hypothalamic-pituitary-adrenal (HPA) axis. Sprague-Dawley rats of both sexes were administered intrarectally with acetic acid. Either leptin (10 mug/kg; i.p.) or saline was injected immediately before and 6 h after the induction of colitis. A group of rats was exposed to water avoidance stress (WAS) for 30 min at the 6th h of colitis induction. RU-486 (2 mg/kg; i.p.), a glucocorticoid receptor antagonist, was injected intraperitoneally, at 12 and 1 h before the initial leptin injection, and at 1 h before the second leptin injection or exposure to WAS. Rats were decapitated at 24 h and the distal 8 cm of,the colon were removed for macroscopic and microscopic scoring, determination of tissue wet weight index (WI) and tissue myeloperoxidase activity (MPO). Acetic acid-induced colitis significantly increased macroscopic and microscopic damage scores, WI and MPO, compared to control group. Exposure to acute WAS or treatment with leptin reduced the elevations in damage scores, WI and MPO induced by colitis, but no additive inhibitory effect was observed when WAS and leptin were applied together. RU-486 treatment reversed the inhibitory effects of leptin or WAS on colonic inflammation. Our results demonstrate that exogenous leptin mimics the effects of HPA axis activation on colitis-induced inflammatory process. The results also suggest that the anti-inflammatory effect of leptin involves a tissue neutrophil-dependent mechanism and is dependent on the release of glucocorticoids. (C) 2003 Elsevier Inc. All rights reserved.