左旋苏糖酸镁减轻肠易激综合征大鼠内脏高敏感性和负性情绪

Magnesium-L-Threonate Allevates Visceral Hypersensitivity and Negative Mood in Irritable Bowel Syndrome Rats

摘要:

目的：探究左旋苏糖酸镁（Magnesium-L-Threonate, L-TAMS）对肠易激综合征（Irritable Bowel Syndrome, IBS）内脏痛及情绪障碍的干预作用。方法：采用新生儿结直肠扩张术构建 IBS 大鼠模型，以每天 604 mg/kg 剂量饮水给予 L-TAMS。通过腹壁撤退反射评分、腹外斜肌肌电记录评估内脏痛敏感性；高架十字迷宫、旷场实验评估焦虑样行为，蔗糖偏好实验评估抑郁样行为；分光光度法检测血清及脑脊液镁离子浓度，Western blot 检测前扣带回皮层（anterior cingulate cortex, ACC）、海马、杏仁核 NMDA 受体亚基 NR1、NR2B 蛋白表达。结果：IBS 大鼠血清与脑脊液游离镁离子显著降低，且与内脏高敏感、负性情绪密切相关；L-TAMS 可恢复镁离子水平，缓解内脏高敏感性，改善焦虑与抑郁样行为，并使 ACC 中异常升高的 NR1、NR2B 表达恢复正常。结论：镁缺乏与 IBS 内脏高敏感及负性情绪相关，L-TAMS 可通过恢复中枢镁稳态、调控 ACC 中 NMDA 受体信号，改善 IBS症状。

Abstract:

Objective: To explore the effects of magnesium-L-threonate (L-TAMS) on visceral pain and emotional disturbances in irritable bowel syndrome (IBS). Methods: IBS rat models were established via neonatal colorectal distension. L-TAMS was administered orally at a daily dose of 604 mg/kg through drinking water. Visceral hypersensitivity was evaluated by abdominal withdrawal reflex scoring and external oblique muscle electromyography. Anxiety-like behaviors were assessed using the elevated plus maze and open field tests, while depression-like behaviors were measured by the sucrose preference test. Serum and cerebrospinal fluid (CSF) Mg2+ concentrations were determined via spectrophotometry. Western blot was used to detect protein expressions of NMDA receptor subunits NR1 and NR2B in the anterior cingulate cortex (ACC), hippocampus, and amygdala. Results: IBS rats exhibited significantly reduced free Mg2+ levels in serum and CSF, which were closely correlated with enhanced visceral hypersensitivity and negative emotional behaviors. L-TAMS treatment effectively restored Mg2+ concentrations, alleviated visceral hypersensitivity, and improved anxiety-and depression-like behaviors. These behavioral improvements were accompanied by normalized expressions of abnormally elevated NR1 and NR2B in the ACC. Conclusion: Magnesium deficiency is associated with visceral hypersensitivity and negative emotional responses in IBS. L-TAMS mitigates these abnormalities, potentially by restoring central magnesium homeostasis and regulating NMDA receptor signaling in the ACC.