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Eosinophil-associated micro-inflammation in the gastroduodenal tract contributes to gastric hypersensitivity in a rat model of early life adversity
American Journal of Physiology-Gastrointestinal and Liver Physiology ( IF 3.9 ) Pub Date : 2020-11-11 , DOI: 10.1152/ajpgi.00313.2020
Shaoqi Duan 1 , Takashi Kondo 2 , Hiroto Miwa 3 , Yanjing Yang 4 , Shenglan Wang 5 , Hirosato Kanda 6 , Yoko Kogure 6 , Nobuko Imamura 7 , Tadahiro Fujimura 7 , Tomoaki Kono 7 , Masashi Fukushima 7 , Katsuyuki Tozawa 7 , Toshihiko Tomita 8 , Tadayuki Oshima 2 , Hirokazu Fukui 1 , Satoshi Yamamoto 6 , Koichi Noguchi 9 , Yi Dai 6
Affiliation  

Gastric hypersensitivity is a major pathophysiological feature of functional dyspepsia (FD). Recent clinical studies have shown that a large number of FD patients present with gastroduodenal micro-inflammation, which may be involved in the pathophysiology of FD. However, no animal model reflecting this clinical characteristic has been established. The underlying mechanism between micro-inflammation and FD remains unknown. In this study, using a maternal separation (MS)-induced FD model, we aimed to reproduce the gastroduodenal micro-inflammation and reveal the interaction between gastroduodenal micro-inflammation and gastric hypersensitivity. The MS model was established by separating newborn Sprague Dawley rats for 2 h a day from postnatal day 1 to day 10. At 7-8 weeks of age, electromyography was used to determine the visceromotor response to gastric distention (GD) and immunohistochemistry was performed to detect distension-associated neuronal activation as well as immunohistological changes. Our results demonstrated that MS-induced FD rats underwent gastric hypersensitivity with GD at 60 and 80 mmHg, which are related to increased p-ERK1/2 expression in the dorsal horn of T9-T10 spinal cords. Eosinophils, but not mast cells, were significantly increased in the gastroduodenal tract, and the co-expression rate of CD11b and major basic protein significantly increased in MS rats. Treatment with dexamethasone reversed gastric hypersensitivity in MS-induced FD rats by inhibiting eosinophil infiltration. These findings indicated that neonatal MS stress induces eosinophil-associated gastroduodenal micro-inflammation and gastric hypersensitivity in adulthood in rats. Micro-inflammation contributes to gastric hypersensitivity; therefore, anti-inflammatory therapy may be effective in treating FD patients with gastroduodenal micro-inflammation.

中文翻译:

胃十二指肠中的嗜酸性粒细胞相关的微炎症在早期生活逆境的大鼠模型中导致胃超敏性

胃超敏反应是功能性消化不良(FD)的主要病理生理特征。最近的临床研究表明,大量FD患者出现胃十二指肠微炎症,可能与FD的病理生理有关。但是,尚未建立反映该临床特征的动物模型。微炎症和FD之间的潜在机制仍然未知。在这项研究中,使用母体分离(MS)诱导的FD模型,我们旨在重现胃十二指肠微炎症,并揭示胃十二指肠微炎症与胃部超敏反应之间的相互作用。通过从出生后的第1天到第10天分离2天内的新生Sprague Dawley大鼠,建立了MS模型。在7-8周龄,肌电图用于确定对胃扩张(GD)的内脏动力反应,并进行免疫组织化学以检测与扩张相关的神经元活化以及免疫组织学变化。我们的研究结果表明,MS诱导的FD大鼠在60和80 mmHg时发生胃超敏性GD,这与T9-T10脊髓背角中p-ERK1 / 2表达增加有关。胃十二指肠中的嗜酸性粒细胞(而非肥大细胞)显着增加,而MS大鼠中CD11b和主要碱性蛋白的共表达率显着增加。地塞米松治疗通过抑制嗜酸性粒细胞浸润逆转了MS诱导的FD大鼠的胃超敏反应。这些发现表明,新生的MS应激在成年大鼠中诱发嗜酸性粒细胞相关的胃十二指肠微炎症和胃超敏反应。微炎症会导致胃过敏。因此,抗炎治疗可能有效治疗患有胃十二指肠微炎症的FD患者。
更新日期:2020-11-12
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