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

我们探讨了褪黑素(ML)保护胃粘膜的机制及其与昼夜节律的关系。我们发现，松果体在应激反应中分泌的ML保护胃粘膜。我们还发现，ML不仅具有外周保护作用，而且还具有中枢保护作用。据推测，这些作用是由脑ML受体Ib介导的。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。黑暗应激组大鼠胃粘膜损伤明显低于光照应激组。轻度应激负荷后，胃粘膜前列腺素(PG)E_2生成量减少。但在暗期，与对照组相比，还原受到抑制。此外，暗周期的ML浓度显著高于光周期…的浓度对照组在应激负荷前d较多，提示与抑制胃损伤有关。COX-2mRNA在应激负荷后的光暗期均有表达，被认为在消化道黏膜损伤修复过程中起重要作用。无论病变数目多少，COX-2mRNA都可能在应激负荷后胃粘膜损伤修复之前出现。这一发现可能反映了应激负荷后胃粘膜前列腺素E_2的生成受到抑制。在摘除松果体的组中，在黑暗时期的应激负荷后，胃粘膜损伤加重。然而，脑池内注射ML可显著抑制病情恶化。这些结果表明，昼夜节律显著影响应激性胃损伤的发生、ML/PGE_2的产生和COX-2mRNA的表达。此外，我们还检测了健康志愿者和胃癌或消化性溃疡患者的血ML和尿ML代谢物水平，证实进展期胃癌患者尿ML代谢物水平降低。在未来，这些参数作为生化标记的有用性应该被研究。较少

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