Multi-targeting regulation of auricular vagus nerve stimulation on gastric hypersensitivity and gastric dysmotility in a rodent model of functional dyspepsia

Peijing Rong, Liwei Hou, Yang Yang, Xiaoying Luo, Junying Wang, Jinling Zhang, Jiande D. Z. Chen, Wei Wei
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Abstract

Background: Evidences have shown the auricular vagus nerve stimulation (aVNS) is effective for functional dyspepsia (FD) recently. This study aimed to observe the mechanism of aVNS on facilitatory mediators of the inflammation in a rat model of functional dyspepsia. Methods: Thirty-six 5 d-old male Sprague Dawley rats were randomly divided into control groups (n = 12), model group (n = 12), aVNS group (n = 6) and sham-aVNS group (n = 6). Except for the control rats, all other rats were treated with iodoacetamide gavage. After the model was developed successfully, rats in aVNS group and sham-aVNS group received aVNS and sham-aVNS respectively, 30 min/1 time per day for 14 consecutive days. The control group and model group received no intervention. Gastric sensitivity after 1-week of intervention and gastric emptying after 2-week of intervention were adopted to assess the effect of aVNS. Brain-gut peptides, facilitatory mediators of the inflammation in serum were tested by ELISA, and α7 nicotinic acetylcholine receptor (α7-nAchR) in antrum tissue were tested by Immunohistochemistry to explore the mechanism of aVNS. Results: Compared with the control group, the gastric sensitivity was increased, gastric emptying decreased, and there was no structural damage in the gastric antrum in the model group. aVNS reduced visceral hypersensitivity and improved gastric emptying but not sham-aVNS. cholecystokinin, glucagon-like peptide-1, peptide, tumor necrosis factorα and interleukin 6 were all increased, while ghrelin and α7-nAchR decreased in model rats (P < 0.01 for all, compared with the control group). aVNS can normalize them. Conclusion: The aVNS can decrease the gastric sensitivity and increase gastric emptying, the mechanism was related to its regulation of brain-gut peptides and facilitatory mediators of the inflammation. The ameliorating effect was related to cholinergic mechanism.
耳迷走神经刺激对功能性消化不良鼠模型胃超敏反应和胃动力障碍的多靶点调控
背景:耳穴迷走神经刺激(aVNS)是治疗功能性消化不良(FD)的有效方法。本研究旨在观察aVNS对功能性消化不良大鼠模型炎症促进介质的作用机制。方法:将36只5 d龄雄性Sprague Dawley大鼠随机分为对照组(n = 12)、模型组(n = 12)、aVNS组(n = 6)和假aVNS组(n = 6),除对照组外,其余大鼠均灌胃碘乙酰胺。造模成功后,aVNS组和假aVNS组大鼠分别给予aVNS和假aVNS,每天30 min/1次,连续14天。对照组和模型组不进行干预。采用干预1周后胃敏感性和干预2周后胃排空情况评价aVNS的效果。采用ELISA法检测血清炎症促进剂脑肠肽,免疫组化法检测上颌窦组织α7烟碱胆碱受体(α7- nachr)水平,探讨aVNS发生的机制。结果:与对照组比较,模型组大鼠胃敏感性增强,胃排空减少,胃窦未见结构性损伤。aVNS减少内脏过敏和改善胃排空,但假aVNS没有。模型大鼠胆囊收缩素、胰高血糖素样肽-1、肽、肿瘤坏死因子α、白细胞介素6均升高,胃饥饿素、α7-nAchR均降低(与对照组比较,P < 0.01)。aVNS可以使它们正常化。结论:aVNS具有降低胃敏感性、增加胃排空的作用,其机制与其调节脑肠肽和炎症促进介质有关。其改善作用与胆碱能机制有关。
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