Anti-inflammatory effects and changes in prostaglandin patterns induced by 7β-hydroxy-epiandrosterone in rats with colitis
Anti-inflammatory effects and changes in prostaglandin patterns induced by 7β-hydroxy-epiandrosterone in rats with colitis
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DOI：
10.1016/j.jsbmb.2007.12.014
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发表时间：
2008-06-01
影响因子：
4.1
通讯作者：
Morfin, Robert
中科院分区：
文献类型：
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作者：
Hennebert, Olivier;Pelissier, Marie-Agnes;Morfin, Robert
研究表明，高剂量的脱氢表雄酮及其7-羟基衍生物可减轻葡聚糖硫酸钠(DSS)诱导的大鼠结肠炎的氧化应激和炎症反应。另一种内源性类固醇7β-羟基表雄酮(7-β-羟基-EPIA)已被证明在较小剂量下具有神经保护作用。我们的目的是评估7β-羟基-EPIA预治疗是否能预防DSS诱导的结肠炎，并确定其作用是否涉及抗炎前列腺素(PG)D-2和15-脱氧-Delta(12，14)-PGJ(2)(15d-PGJ(2))水平的变化。大鼠腹腔注射7β-羟基-EPIA 0.01、0.1和1 mg/kg。每天一次，连续7天。然后，在饮水中加入5%DSS，连续7d诱导大鼠结肠炎。在实验过程中检测PGs水平以及环氧合酶(COX-2)和PG合成酶的表达。给予7β-羟基-EPIA后，COX-2和PGE合成酶的表达在6-15小时内一过性增加，15d-PGJ(2)水平从第二天开始升高。DSS治疗导致结肠长度缩短，杯状细胞内粘液耗竭，并诱导氧化应激。COX-2和mPGES-1合酶表达增强，并伴有PGE(2)、D-2和15d-PGJ(2)产生增加。尽管所有剂量水平的7β-羟基-EPIA都减少了前列腺素E(2)的产生，但只有最低剂量(0.01毫克/公斤)的类固醇完全防止了结肠炎和组织炎症。7β-羟基-EPIA预治疗通过将PGE(2)转变为PGD(2)来预防DSS诱导的结肠炎的发生，与COX-2表达的早期和一过性增加以及抗炎前列腺素15d-PGJ(2)的产生持续增加有关。(C)2008爱思唯尔有限公司。保留所有权利。
High dose levels of dehydroepiandrosterone and its 7-hydroxylated derivatives have been shown to reduce oxidative stress and inflammatory responses in dextran sodium sulfate (DSS)-induced colitis in rats. Another endogenous steroid, 7 beta-hydroxy-epiandrosterone (7 beta-hydroxy-EpiA) has been shown to exert neuroprotective effects at much smaller doses. Our aims were to evaluate whether 7 beta-hydroxy-EpiA pre-treatment prevents DSS-induced colitis and to determine whether the effects involve changes in anti-inflammatory prostaglandin (PG) D-2 and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) levels. Rats were administered 0.01, 0.1 and 1 mg/kg 7 beta-hydroxy-EpiA i.p. once a day for 7 days. Thereafter, colitis was induced by administration of 5% DSS in drinking water for 7 days. Levels of the PGs and the expression of cyclooxygenase (COX-2) and PG synthases were assessed during the course of the experiment. Administration of 7 beta-hydroxy-EpiA caused a transient increase in COX-2 and PGE synthase expression within 6-15 h and augmented colonic tissue levels of 15d-PGJ(2) levels starting at day 2. Treatment with DSS resulted in shortened colon length, depleted mucus in goblet cells and induced oxidative stress. COX-2 and mPGES-1 synthase expression were enhanced and accompanied by increased PGE(2), D-2 and 15d-PGJ(2) production. Although all dose levels of 7 beta-hydroxy-EpiA reduced PGE(2) production, only the lowest dose (0.01 mg/kg) of the steroid completely prevented colitis damage and tissue inflammation. 7 beta-Hydroxy-EpiA pre-treatment prevents the occurrence of DSS-induced colitis through a shift from PGE(2) to PGD(2) production, associated with an early but transient increase in COX-2 expression and a sustained increase in the production of the anti-inflammatory prostaglandin 15d-PGJ(2). (C) 2008 Elsevier Ltd. All rights reserved.