Wang Xiaobo, Shao Limei, Hua Hongjun, Chen Yanping
The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Gastroenterology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China.
Ann Transl Med. 2023 Jan 31;11(2):118. doi: 10.21037/atm-22-6452.
Visceral hypersensitivity (VH) is one of the most common causes of irritable bowel syndrome (IBS). The anti-hyperalgesic effects of metabotropic glutamate receptor 8 (mGluR8) has been identified in the central nervous system (CNS). However, whether this receptor has a similar function in the gastrointestinal tract has not been well studied. The present study aimed to explore the role of this receptor in a visceral hypersensitivity-related IBS rat model.
Neonatal rats were separated from their mothers for 3 hours daily from postnatal day 2 to day 14 to establish neonatal maternal separation (NMS) models. The mGluR8 agonist (S)-3,4-DCPG (10 mg/kg) and the mGluR8 antagonist (RS)-α- methylserine-O-phosphate (MSOP) (10 mg/kg) were used to examine the role of mGLuR8 in the NMS rats. The expression of mGluR8, related inflammatory factors, and inflammatory signal pathways were assessed in colon tissues.
Our data showed that mGluR8 expression was increased in the colonic mucosa of NMS rats compared to controls. In addition, selective activation of mGluR8 ameliorated visceral hypersensitivity, whereas antagonization of mGluR8 aggravated visceral hypersensitivity. Treatment with (S)-3,4-DCPG (10 mg/kg) reduced the expression of myeloperoxidase (MPO) in intestinal mucosa of NMS rats. Furthermore, activating mGluR8 reduced the expression of tumor necrosis factor-α (TNF-α), whereas antagonizing mGluR8 promoted that. The expressions of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) did not significantly change upon activation or antagonization of mGluR8 receptor.
The activation of mGluR8 receptor ameliorates visceral hypersensitivity in NMS rats, and the underlying mechanisms may be associated with the inhibition of TNF-α and the suppression of colonic inflammatory response.
内脏高敏感性（VH）是肠易激综合征（IBS）最常见的病因之一。代谢型谷氨酸受体8（mGluR8）在中枢神经系统（CNS）中的抗痛觉过敏作用已得到证实。然而，该受体在胃肠道中是否具有类似功能尚未得到充分研究。本研究旨在探讨该受体在内脏高敏感性相关的IBS大鼠模型中的作用。
从出生后第2天至第14天，每天将新生大鼠与其母亲分离3小时，以建立新生鼠母婴分离（NMS）模型。使用mGluR8激动剂（S）-3,4-二氯苯基甘氨酸（10 mg/kg）和mGluR8拮抗剂（RS）-α-甲基丝氨酸-O-磷酸（MSOP）（10 mg/kg）来研究mGLuR8在NMS大鼠中的作用。评估结肠组织中mGluR8、相关炎症因子及炎症信号通路的表达。
我们的数据显示，与对照组相比，NMS大鼠结肠黏膜中mGluR8表达增加。此外，mGluR8的选择性激活改善了内脏高敏感性，而mGluR8的拮抗作用则加重了内脏高敏感性。用（S）-3,4-二氯苯基甘氨酸（10 mg/kg）处理可降低NMS大鼠肠黏膜中髓过氧化物酶（MPO）的表达。此外，激活mGluR8可降低肿瘤坏死因子-α（TNF-α）的表达，而拮抗mGluR8则促进其表达。mGluR8受体激活或拮抗后，Toll样受体4（TLR4）和核因子-κB（NF-κB）的表达无明显变化。
mGluR8受体的激活改善了NMS大鼠的内脏高敏感性，其潜在机制可能与抑制TNF-α及抑制结肠炎症反应有关。
