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

本文探讨了褪黑素（ML）保护胃粘膜的机制及其与昼夜节律的关系。我们发现，ML，这是由松果体分泌的应激反应，保护胃粘膜。我们还发现，ML不仅表现出周边，而且中央胃粘膜保护行动。有人认为，这些行动是由大脑ML受体介导的，Ib。在与昼夜节律的关系方面，在光/暗期间给予大鼠浸水限制应激。在黑暗期应激组中，胃病变比在光照期应激组中显著抑制。胃粘膜前列腺素E_2（PG E_2）的产生在应激负荷后减少。然而，在黑暗时期，减少被抑制相比，在对照组。此外，暗期的ML浓度显著高于亮期， ...更多信息 d，提示与抑制胃病变有关。应激负荷后，在光照和黑暗两个时间段均可检测到考克斯-2 mRNA的表达，COX-2在消化道黏膜损伤修复过程中起重要作用。无论损伤数量多少，应激负荷后，考克斯-2 mRNA可能先于胃粘膜损伤修复出现。这一结果可能反映了应激负荷后胃粘膜PGE_2的产生受到抑制。在松果体摘除组中，胃粘膜病变加重后，在黑暗期间的应力负荷。然而，脑池内预处理ML可显著抑制急性加重。提示昼夜节律显著影响应激性胃粘膜损伤的发生、ML/PGE_2的产生及考克斯-2 mRNA的表达。此外，在健康志愿者和胃癌或消化性溃疡患者中测量了血ML和尿ML代谢物水平，我们证实了晚期胃癌患者的尿ML代谢物水平降低。在未来，这些参数作为生化标志物的有用性应进行调查。少

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

Otsuka M, Kato K, Imurai I, et al.: "Roles of nocturnal melatonin and pineal gland in modulation of water-immersion restraint stress-induced gastric mucosal lesions in rats"J Pineal Research. 30. 82-86 (2001)

Otsuka M、Kato K、Imurai I 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。