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胃食管反流病动物模型方法的比较分析:过去十年的数据挖掘

Comparative Analysis of Gastroesophageal Reflux Disease Animal Model Methods: A Data Mining of the Past Decade.

作者信息

Lv Mi, Huang Kai-Yue, Wang Xiao-Kang, Wang Yu-Xi, Qiao Xi-Yun, Che Hui, Lv Lin, Wang Feng-Yun

机构信息

Xiyuan Hospital, China Academy of Traditional Chinese Medicine, No. 1 Xiyuan Playground, Haidian District, Beijing, 100091, China.

Beijing University of Chinese Medicine, Beisanhuan East Road, Chaoyang District, Beijing, 100029, China.

出版信息

Dig Dis Sci. 2025 Apr 1. doi: 10.1007/s10620-025-09022-x.

DOI:10.1007/s10620-025-09022-x
PMID:40167947
Abstract

PURPOSE

The differences in the animal model construction of different subtypes of gastroesophageal reflux disease (GERD) have not been clearly demonstrated at present. We aim to reveal the characteristics and differences between them.

METHODS

The literature related to GERD animal model construction in the past decade was searched and data on animal strains, modeling modes, modeling cycles, and detection indices were extracted, and the results were presented by using descriptive statistical methods of frequency and relative frequency.

RESULTS

88 papers finally met the criteria. Sprague-Dawley (68.25%) rats were most often used to induce reflux esophagitis (RE), whereas Swiss mice (50.00%) and C57BL/6 mice (57.89%) for non-erosive reflux disease (NERD) and Barrett's esophagus (BE), respectively. RE and NERD were most frequently constructed using fore-stomach-glandular transition ligation together with pyloric insufficiency (37.68%, 50.00%), yet their median modeling cycles were 14 and 7 days, respectively. BE was most frequently constructed using L2-IL-1β transgenic mice (27.27%), and the median modeling cycle over 270 days. Determining esophageal mucosal permeability was common in NERD, while finding intestinal chemotaxis markers, squamous epithelium, and columnar epithelium was common in BE. In animal models of RE, researchers tended to look for markers associated with the inflammatory response and oxidative stress.

CONCLUSIONS

The induction methods vary among the animal models of GERD's three subtypes. Inflammatory stimulation is crucial for inducing RE and BE, differing in modeling cycle. In contrast, Visceral hypersensitivity draws more attention in NERD animal models, reflecting researchers' thoughts on distinct pathogenesis.

摘要

目的

目前不同亚型胃食管反流病(GERD)动物模型构建的差异尚未明确阐明。我们旨在揭示它们之间的特征和差异。

方法

检索过去十年中与GERD动物模型构建相关的文献,提取动物品系、建模方式、建模周期和检测指标的数据,并采用频率和相对频率的描述性统计方法呈现结果。

结果

最终88篇论文符合标准。Sprague-Dawley大鼠(68.25%)最常用于诱导反流性食管炎(RE),而瑞士小鼠(50.00%)和C57BL/6小鼠(57.89%)分别用于非糜烂性反流病(NERD)和巴雷特食管(BE)的模型构建。RE和NERD最常采用前胃-腺过渡结扎联合幽门功能不全构建(分别为37.68%、50.00%),但其建模周期中位数分别为14天和7天。BE最常采用L2-IL-1β转基因小鼠构建(27.27%),建模周期中位数超过270天。在NERD中,测定食管黏膜通透性较为常见,而在BE中,寻找肠道趋化标记物、鳞状上皮和柱状上皮较为常见。在RE动物模型中,研究人员倾向于寻找与炎症反应和氧化应激相关的标记物。

结论

GERD三种亚型的动物模型诱导方法各不相同。炎症刺激对诱导RE和BE至关重要,建模周期有所不同。相比之下,内脏高敏感性在NERD动物模型中更受关注,反映了研究人员对不同发病机制的思考。

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本文引用的文献

1
Bidirectional correlation between gastroesophageal reflux disease and sleep problems: a systematic review and meta-analysis.胃食管反流病与睡眠问题之间的双向相关性:一项系统评价和荟萃分析。
PeerJ. 2024 Apr 16;12:e17202. doi: 10.7717/peerj.17202. eCollection 2024.
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Gastroesophageal reflux disease with 6 neurodegenerative and psychiatric disorders: Genetic correlations, causality, and potential molecular mechanisms.胃食管反流病伴发 6 种神经退行性和精神障碍:遗传相关性、因果关系及潜在分子机制。
J Psychiatr Res. 2024 Apr;172:244-253. doi: 10.1016/j.jpsychires.2024.02.030. Epub 2024 Feb 13.
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Atractylenolide III ameliorated reflux esophagitis via PI3K/AKT/NF-κB/iNOS pathway in rats.
白术内酯III通过PI3K/AKT/NF-κB/iNOS通路改善大鼠反流性食管炎。
Heliyon. 2023 Oct 23;9(11):e21224. doi: 10.1016/j.heliyon.2023.e21224. eCollection 2023 Nov.
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Therapeutic Effect of Polaprezinc on Reflux Esophagitis in the Rat Model.聚普瑞锌治疗大鼠反流性食管炎的疗效观察。
Dig Dis Sci. 2023 Aug;68(8):3283-3292. doi: 10.1007/s10620-023-07990-6. Epub 2023 Jun 19.
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JP-1366: A novel and potent potassium-competitive acid blocker that is effective in the treatment of acid-related diseases.JP-1366:一种新型强效钾离子竞争性酸阻滞剂,可有效治疗酸相关疾病。
Pharmacol Res Perspect. 2023 Jun;11(3):e01090. doi: 10.1002/prp2.1090.
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Dynorphin participates in interaction between depression and non-erosive reflux disease.脑啡肽参与抑郁和非糜烂性反流病的相互作用。
Esophagus. 2023 Jan;20(1):158-169. doi: 10.1007/s10388-022-00955-0. Epub 2022 Oct 16.
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Proteomic analysis reveals that ACSL4 activation during reflux esophagitis contributes to ferroptosis-mediated esophageal mucosal damage.蛋白质组学分析表明,反流性食管炎中 ACSL4 的激活有助于铁死亡介导的食管黏膜损伤。
Eur J Pharmacol. 2022 Sep 15;931:175175. doi: 10.1016/j.ejphar.2022.175175. Epub 2022 Jul 31.
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Global, regional and national burden of gastroesophageal reflux disease, 1990-2019: update from the GBD 2019 study.全球、区域和国家胃食管反流病负担,1990-2019 年:来自 GBD 2019 研究的更新。
Ann Med. 2022 Dec;54(1):1372-1384. doi: 10.1080/07853890.2022.2074535.
9
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Evid Based Complement Alternat Med. 2022 Jan 4;2022:6969241. doi: 10.1155/2022/6969241. eCollection 2022.
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Dis Esophagus. 2022 May 10;35(5). doi: 10.1093/dote/doab072.