摘要
背景胃黏膜诱生型一氧化氮合酶(iNOS)的过度表达在应激性溃疡的发生中起重要作用。目的研究褪黑激素(MT)对水浸鄄束缚应激大鼠胃黏膜iNOS表达的影响及其对胃黏膜的保护作用,以进一步阐明MT的作用机制。方法正常对照组不予水浸鄄束缚应激和MT预防,模型组和MT低剂量预防组、MT高剂量预防组于应激前30min分别腹腔注射含1%二甲基亚砜(DMSO)或MT5mg/kg、20mg/kg的等体积生理盐水。应激6h后处死动物,检测各组大鼠胃黏膜一氧化氮(NO)水平、iNOS蛋白和iNOSmRNA的表达,并评估胃黏膜损伤程度。结果水浸鄄束缚应激6h后,大鼠胃黏膜NO水平、iNOS蛋白和iNOSmRNA表达显著增加,胃黏膜病变明显。MT预防组大鼠胃黏膜NO水平、iNOS蛋白和iNOSmRNA表达均显著低于模型组(P<0.01),且溃疡指数(UI)显著下降(P<0.01)。MT高剂量预防组大鼠各检测指标均显著低于MT低剂量预防组(P<0.05),作用呈剂量依赖性。结论MT可预防水浸鄄束缚应激诱导的大鼠胃黏膜损伤,其机制可能与其抑制胃黏膜iNOS过度表达有关。
Background: The overexpression of inducible nitric oxide synthase (iNOS) in gastric mucosa is responsible for the development of gastric stress ulcer. Aims: To investigate the protective effects of melatonin on the expression of iNOS in gastric mucosa of rats with water-immersion restraint induced ulcer, and to elucidate its mechanism of action. Methods: Melatonin (5 mg/kg or 20 mg/kg) was injected intraperitoneally 30 min before water-immersion restraint stress and the rats were killed 6 h after the stress. The gastric mucosal lesions were evaluated macroscopically and nitric-oxide (NO) levels and expression of iNOS protein and mRNA in gastric mucosa were detected. Results: Water-immersion restraint stress caused significant gastric lesions associated with a significant rise of the levels of NO and the expression of iNOS protein and mRNA in gastric mucosa. Whilst the NO level and expression of iNOS protein and mRNA in gastric mucosa in melatonin administered rats were significiantly lower than that in controls (P<0.01), and associated with marked decrease of ulcer index(P<0.01). Melatonin administration counteracted significantly with these tissue and metabolic alterations in a dose-dependent manner. Conclusions: Melatonin can inhibit iNOS expression and the subsequent NO production in gastric mucosa of water-immersion restraint stress rat, which may account for the protection of the melatonin against water-immersion restraint stress.
出处
《胃肠病学》
2004年第5期270-273,共4页
Chinese Journal of Gastroenterology
基金
温州市科学技术局(No.Y2003A023)资助
