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催产素通过γ-氨基丁酸B1型受体-瞬时受体电位香草酸亚型1缓解肠易激综合征大鼠内脏痛(英文)

范飞^1,2, 曹阳^2,3, 何正庆², 杨凡², 陈瑜², 陈爱琴², 林春^2,*

¹福建卫生职业技术学院，福州 350101；²福建医科大学基础医学院疼痛研究所；福建省脑老化与神经变性疾病重点实验室， 福州 350122；³浙江省义乌市中心医院，义乌 322000

摘要

催产素已被证实能够调节并改善人类疼痛感知，但其在内脏痛觉敏感性中发挥镇痛作用的具体机制尚不明确。本研究通过对8~14日龄新生大鼠采用结直肠扩张刺激建立肠易激综合征(irritable bowel syndrome, IBS)模型，应用腹外斜肌对结直肠扩张刺激的放电幅值评估内脏痛觉敏感性。脊髓鞘内置管给予不同剂量催产素或γ-氨基丁酸B1 型受体(γ-aminobutyric acidtype B1 receptor, GABAB1)拮抗剂沙洛芬(saclofen)，观察其对大鼠内脏痛的影响。免疫印迹法检测大鼠脊髓腰骶段催产素受体(oxytocin receptor, OTR)、GABAB1、瞬时受体电位香草酸亚型1 (transient receptor potential vanilloid 1, TRPV1)的表达。结果显示，IBS 大鼠OTR与GABAB1 表达降低，而TRPV1 表达增加；鞘内注射催产素可减轻内脏痛，并使GABAB1 表达增加，TRPV1 表达降低，沙洛芬可逆转催产素的作用。以上结果表明催产素可通过GABAB1-TRPV1 缓解IBS大鼠内脏痛。

关键词： 肠易激综合征; 催产素受体; TRPV1; γ-氨基丁酸B1型受体; 内脏痛; 脊髓

Oxytocin relieves visceral hypersensitivity through GABAB1-TRPV1 in rats with irritable bowel syndrome

FAN Fei^1,2, CAO Yang^2,3, HE Zheng-Qing², YANG Fan², CHEN Yu², CHEN Ai-Qin², LIN Chun^2,*

¹Fujian Health College, Fuzhou 350101, China；²Institute of Pain Research, School of Basic Medical Sciences, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Medical University, Fuzhou 350122, China ；³Yiwu Central Hospital, Yiwu 322000, China

Abstract

Oxytocin has been found to modulate and improve pain in humans, but the mechanisms underlying these antinociceptive properties, especially in visceral hypersensitivity, are still unclear. Irritable bowel syndrome (IBS) models were established by colorectal distention in newborn rats aged 8 to 14 days, and visceral hypersensitivity was assessed using electromyogram (EMG). Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats. The protein expressions of oxytocin receptor (OTR), γ-aminobutyric acid type B1 receptor (GABAB1), and transient receptor potential vanilloid 1 (TRPV1) in the lumbosacral spinal cord regions were measured. IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression. Intrathecal oxytocin treatment not only normalized these molecular alterations (increasing GABAB1 while decreasing TRPV1) but also ameliorated visceral pain behaviors. Crucially, this therapeutic effect was fully reversed by GABAB1 inhibition, establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia. Collectively, these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.

Key words: irritable bowel syndrome; oxytocin receptor; TRPV1; GABAB1; visceral hypersensitivity; spinal cord

收稿日期：　　录用日期：

通讯作者：林春　　E-mail:

DOI: 10.13294/j.aps.2025.0102

引用本文：

范飞, 曹阳, 何正庆, 杨凡, 陈瑜, 陈爱琴, 林春. 催产素通过γ-氨基丁酸B1型受体-瞬时受体电位香草酸亚型1缓解肠易激综合征大鼠内脏痛(英文)[J]. 生理学报 2026; 78 (1): 173-181.

FAN Fei, CAO Yang, HE Zheng-Qing, YANG Fan, CHEN Yu, CHEN Ai-Qin, LIN Chun. Oxytocin relieves visceral hypersensitivity through GABAB1-TRPV1 in rats with irritable bowel syndrome. Acta Physiol Sin 2026; 78 (1): 173-181