Pei Xinyao, Ma Yue, Gu Jingyan, He Xueyun, Lu Yanyu, Wang Yudong, Hao Xujiang, Tao Yongbiao, Li Hongfang
Department of Physiology, College of Basic Medicine, Lanzhou University, Lanzhou, China.
Function Laboratory in College of Basic Medicine, Lanzhou University, Lanzhou, Gansu, China.
Neurogastroenterol Motil. 2025 Sep;37(9):e70070. doi: 10.1111/nmo.70070. Epub 2025 May 2.
The long-term recurrent symptoms of functional dyspepsia (FD) and the prolonged course of the disease lead to varying degrees of psychological disorders in patients. The study focuses on investigating the effects of the psychological drug amitriptyline on FD rats, aiming to provide a basis for the mechanism of action in treating FD from a clinical psychological perspective.
A rat model of FD was used to assess gastric emptying, intestinal propulsion, visceral sensitivity, and behavioral states after treatment with amitriptyline, domperidone, or both drugs. The concentrations of 5-hydroxytryptamine (5-HT) and the expression of related signaling molecules were measured using ELISA, RT-qPCR, and Western blot. Gastrointestinal motility was also evaluated through muscle perfusion experiments, and the composition of gut microbiota was analyzed using 16S rRNA sequencing.
Amitriptyline, either alone or combined with domperidone, improved FD rat behavioral scores, food intake, and mental status in FD rats. It increased 5-HT concentrations in plasma and gastrointestinal tissue, decreased visceral sensitivity, and altered the expressions of 5-HT2B receptor, phospholipase C-β, IP receptor, and calcium-activated chloride channel anoctamin 1 (ANO1) in the gastrointestinal tissues. Although amitriptyline had no significant effect on in vivo gastric or intestinal transit rates, it significantly inhibited the contractile activity of isolated gastrointestinal muscle strips and exhibited anticholinergic effects. Additionally, amitriptyline either alone or combined with domperidone increased the relative abundance of Actinomycetota and specifically the Eggerthellales order in the gut microbiota.
The combination of amitriptyline and domperidone relieves anxiety and depression, improves gastrointestinal motility by targeting the 5-HT2BR, PLCβ, and IPR signaling pathways, and modulates the gut microbiota. This integrated approach alleviates FD symptoms through multiple mechanisms and pathways, presenting a promising therapeutic strategy.
功能性消化不良（FD）的长期复发症状及病程迁延导致患者出现不同程度的心理障碍。本研究聚焦于探究抗抑郁药阿米替林对FD大鼠的影响，旨在从临床心理学角度为治疗FD的作用机制提供依据。
采用FD大鼠模型，评估阿米替林、多潘立酮或两种药物联合治疗后的胃排空、肠推进、内脏敏感性和行为状态。使用酶联免疫吸附测定（ELISA）、逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法检测5-羟色胺（5-HT）浓度及相关信号分子的表达。通过肌肉灌注实验评估胃肠动力，并采用16S核糖体RNA测序分析肠道微生物群的组成。
阿米替林单独使用或与多潘立酮联合使用，均可改善FD大鼠的行为评分、食物摄入量和精神状态。它可提高血浆和胃肠组织中的5-HT浓度，降低内脏敏感性，并改变胃肠组织中5-HT2B受体、磷脂酶C-β、IP受体和钙激活氯离子通道anoctamin 1（ANO1）的表达。尽管阿米替林对体内胃或肠道转运率无显著影响，但它可显著抑制离体胃肠肌条的收缩活性，并表现出抗胆碱能作用。此外，阿米替林单独使用或与多潘立酮联合使用均可增加放线菌门的相对丰度，特别是肠道微生物群中埃格特菌目的丰度。
阿米替林与多潘立酮联合使用可缓解焦虑和抑郁，通过靶向5-HT2BR、PLCβ和IPR信号通路改善胃肠动力，并调节肠道微生物群。这种综合方法通过多种机制和途径缓解FD症状，是一种有前景的治疗策略。
