Abstract Context: A growing body of evidence demonstrates that gastrointestinal motility disorder (GIMD) and gastric stress ulcers can be induced by restraint stress, while melatonin (MT) elicits anti-inflammation and antioxidant effects. Objective: The present study investigated the mechanisms of MT-mediated protection effects on restraint stress-induced GIMD. Materials and methods: 144 8-week-old male ICR mice were divided into four groups: control, restraint stress, restraint stress + MT and MT (positive control). 20 mg/kg MT or vehicle were intraperitoneally injected 60 min before restraint stress (10 h/day) once daily for 3 days. Biochemical parameters, intestinal mucosal integrity, tissues antioxidant ability and autophagic proteins levels were determined. Results: Mice subjected to restraint stress elevated NE level by 141.41% and decreased MT content by 38.82% in plasma. Consistent with the decrease in MT level, we observed a reduction in the antioxidant ability and an increase in autophagic proteins by 14.29–46.74% in the gut, resulting in injury to intestinal mucosa which was manifested by reductions in villus height and villus height/crypt depth (V/C) ratio, number of goblet and PCAN-positive cells, and expression of tight junction protein (ZO-1, occludin and claudin-1). In contrast, MT reversed these changes caused by restraint stress and improved the intestinal mucosal injury. However, there was no significant difference between MT (positive control) and control group. Discussion and conclusion: Our results suggest that MT effectively mitigates psychological stress-induced injury to intestinal mucosa, providing evidence demonstrating the potential for using MT as therapy against intestinal impairment associated with psychological stress.

中文翻译：

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褪黑激素在束缚应激所致小鼠肠黏膜损伤中的作用

摘要背景：越来越多的证据表明，束缚应激可诱发胃肠动力障碍（GIMD）和胃应激性溃疡，而褪黑激素（MT）则具有抗炎和抗氧化作用。目的：本研究调查了 MT 介导的保护作用对约束应激诱导的 GIMD 的机制。材料与方法：144只8周龄雄性ICR小鼠分为4组：对照、束缚应激、束缚应激+MT和MT（阳性对照）。20 mg/kg MT 或载体在束缚应激（10 小时/天）前 60 分钟腹膜内注射，每天一次，持续 3 天。测定生化参数、肠粘膜完整性、组织抗氧化能力和自噬蛋白水平。结果：受到束缚应激的小鼠的 NE 水平提高了 141。41%，血浆中 MT 含量降低 38.82%。与 MT 水平的降低一致，我们观察到肠道中抗氧化能力降低和自噬蛋白增加 14.29-46.74%，导致肠粘膜损伤，表现为绒毛高度和绒毛高度/隐窝降低深度 (V/C) 比、杯状细胞和 PCAN 阳性细胞的数量以及紧密连接蛋白（ZO-1、occludin 和 claudin-1）的表达。相比之下，MT 逆转了这些由束缚应力引起的变化并改善了肠粘膜损伤。然而，MT（阳性对照）和对照组之间没有显着差异。讨论与结论：我们的研究结果表明，MT 可有效减轻心理压力引起的肠黏膜损伤，