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

基本信息

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

项目摘要

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) 保护胃粘膜的机制以及与昼夜节律的关系，我们发现松果体在应激时分泌的 ML 可以保护胃粘膜。就与昼夜节律、水浸限制应激的关系而言，这些作用是由大脑 ML 受体介导的。在光照/黑暗期间给予大鼠，在黑暗期间应激组中，胃损伤比在光照期间应激组中受到显着抑制，在应激负荷后，胃粘膜前列腺素（PG）E_2的产生减少。然而，在黑暗时期，与对照组相比，减少受到抑制，并且在应激前的对照组中，黑暗时期ML的浓度显着高于光照时期。加载中，建议与抑制胃损伤相关，据报道，COX-2 mRNA 在消化道粘膜损伤的修复过程中发挥着重要作用，无论在压力负荷后的光照和黑暗时期均检测到。损伤的数量，COX-2 mRNA可能出现在应激负荷后胃粘膜损伤修复之前，这一发现可能反映了在松果体被摘除的组中，胃粘膜PGE_2的产生受到抑制。黑暗期应激负荷后胃粘膜病变加剧，但脑池内 ML 预处理可显着抑制恶化。这些结果表明，昼夜节律显着影响应激诱发的胃病变的发展、ML/PGE_2 的产生和 COX-2。此外，我们还测量了健康志愿者和胃癌或消化性溃疡患者的血液 ML 和尿 ML 代谢物水平，并证实尿 ML 存在。晚期胃癌患者的代谢水平降低，未来应研究这些参数作为生化标志物的作用。