ROLES OF DIURNAL RHYTHM AND PINEAL HORMONE MELATONIN, IN THE GASTRIC MUCOSA PROTECTING MECHANISM

昼夜节律和松果体激素褪黑激素在胃粘膜保护机制中的作用

• 批准号: 12670524
• 负责人: KATO Kimitoshi
• 金额: $ 2.18万
• 依托单位: Nihon University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670524/
• 关键词: melatonin; pineal gland; stress ulcer; gastric lesion; Circadian rhythm; PGE2; Cox; サーカデイアンリズム

We investigated the mechanism by which melatonin (ML) protected the gastric mucosa and the relation to diurnal rhythm. We found that ML, which is secreted by the pineal body in response to stress, protects the gastric mucosa. We also found that ML showed not only peripheral but also central gastric mucosa-protecting actions. It was suggested that these actions are mediated by a brain ML receptor, Ib. With respect to the relation to diurnal rhythm, water-immersion restriction stress was given to rats during the light/dark periods. In the group with stress during the dark period, gastric lesions were significantly inhibited than in the group with stress during the light period. Gastric mucosa prostaglandin (PG)E_2 production reduced after stress loading during the light period. However, during the dark period, reduction was inhibited compared to that in the control group. Furthermore, the concentration of ML during the dark period was significantly higher than that during the light perio … More d in the control group before stress loading, suggesting the association with inhibition of gastric lesions. The expression of COX-2 mRNA, which has been reported to play an important role in the repair process of digestive tract mucosal injury, was detected during both the light and dark periods after stress loading. Regardless of the number of lesions, COX-2 mRNA may appear prior to repair of gastric mucosal lesions after stress loading. This finding may reflect inhibition of gastric mucosa PGE_2 production after stress loading. In the group in which the pineal body was extirpated, gastric mucosal lesions exacerbated after stress loading during the dark period. However, exacerbation was significantly inhibited by intracisternal pretreatment with ML. These findings suggest that diurnal rhythm markedly influences the development of stress-induced gastric lesions, ML/PGE_2 production, and COX-2 mRNA expression. Furthermore, blood ML and urinary ML metabolite levels were measured in healthy volunteers and patients with gastric cancer or digestive ulcer, and we confirmed that urinary ML metabolite levels were decreased in patients with advanced gastric cancer. In the future, the usefulness of these parameters as biochemical markers should be investigated. Less

我们研究了褪黑激素（ML）保护胃粘膜以及与不同节奏的关系的机制。我们发现由松果体响应压力分泌的ML保护胃粘膜。我们还发现，ML不仅显示外围，而且显示中央胃粘膜保护作用。有人建议这些动作是由脑ML受体IB介导的。关于与不同节奏的关系，在光/黑暗时期内给大鼠施加了限制压力。在黑暗时期应力的组中，胃病变受到明显的抑制，而在光期间的应力。胃粘膜前列腺素（PG）E_2在光期间载荷后的产生减少。然而，在黑暗时期，与对照组相比，还原抑制了。此外，黑暗时期内ML的浓度明显高于光周期的浓度……在压力加载之前，对照组中的d浓度更多，这表明与胃病变的抑制相关。据报道，在压力负荷后的光和黑暗时期都检测到Cox-2 mRNA的表达在消化道粘膜损伤的修复过程中起重要作用。不管病变的数量多少，在应激负荷后修复胃粘膜病变之前，COX-2 mRNA可能会出现。这一发现可能反映了压力加载后胃粘膜PGE_2产生的抑制作用。在脱离松果体的组中，在黑暗时期应力载荷后，胃粘膜病变加剧了。然而，通过用ML进行内预处理可显着抑制恶化。这些发现表明，昼夜节奏明显影响应激诱导的胃病变，ML/PGE_2产生和COX-2 mRNA表达的发展。此外，在健康的志愿者和胃癌或消化溃疡患者中测量了血液ML和尿液ML代谢物水平，我们确认晚期胃癌患者的尿液ML代谢物水平得到了改善。将来，应研究这些参数作为生化标记的有用性。较少的

项目成果

Kato K, Murai I, Asai S, et al.: "The circadian rhythm of melatonin and prostaglandin in modulation of water-immersion restraint stress-induced gastric mucosal lesions in rats"Alim Pharmaceutical & Therapeutics. 16(2). 29-34 (2002)

Kato K、Murai I、Asai S 等人：“褪黑素和前列腺素的昼夜节律在调节大鼠水浸束缚应激诱发的胃粘膜病变中”Alim Pharmaceutical

Otsuka, Kato, Murai, Asai et al.: "Roles of noctumal melatonin and the pineal gland in modulation of water-immersion restraint stress-induced gastric mucosal lesions in rats"J Pineal Research. 30. 82-86 (2001)

Otsuka、Kato、Murai、Asai 等人：“夜间褪黑激素和松果体在调节水浸束缚应激诱发的大鼠胃粘膜病变中的作用”J Pineal Research。

Kato K, Asai S, Murai I et al.: "Melatonin's gastroprotective and anti-stress role involves both central and peripheral sites"J of Gastroentrology. 36(2). 91-95 (2001)

Kato K、Asai S、Murai I 等人：“褪黑素的胃肠保护和抗应激作用涉及中枢和外周部位”J of Gastroentrology。

Kato K, Murai I, Asai S et al.: "Circadian rhythm of melatonin and prostaglandin ill modulation of stress-induced gastric mucosal lesions in rats"Alimentary Pharmaceutical & Therapeutics. 16(2). 29-34 (2002)

Kato K、Murai I、Asai S 等人：“褪黑激素和前列腺素的昼夜节律对大鼠应激性胃粘膜损伤的调节不良”消化制药

加藤公敏,浅井聡,村井一郎 他: "松果体ホルモン(メラトニン)のレセプターを介した中枢性胃粘膜保護作用について"実験潰瘍. 27(1). 42-43 (2000)

Kimitoshi Kato、Satoshi Asai、Ichiro Murai 等人：“松果体激素（褪黑激素）受体介导的中央胃粘膜保护作用”实验性溃疡 27(1)。