Su Tian, Zhou Li, Peng Bingyan, Du Wei, Liu Xin, Li Ziyu, Zhao Yani, Han Xinjie, Liu Changchang, Wang Zhiyong
Department of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
Mol Biol Rep. 2025 Mar 24;52(1):335. doi: 10.1007/s11033-025-10457-8.
Nonsteroidal anti-inflammatory drugs induced enteropathy is characterized by disruption of the epithelial barrier and immune homeostasis, resulting in symptoms such as congestion, ulcers and inflammation. Research has suggested that dopamine (DA) exerts a protective effect on the gastroduodenal and colonic mucosa. The present study aimed to explore the effect of DA on NSAID-induced injury to the small intestinal mucosa.
A mouse model of enteropathy induced by indomethacin (Indo, which is a commonly used NSAID) was established by gavage. The DA agonist rotigotine (Roti) was administered alone or in combination with the DA receptor 2 (DRD2) antagonist domperidone (Domp) to model mice to determine the effect of Roti and the key role of DRD2 in this effect. Bilateral vagotomy was performed to determine whether the effect of Roti was mediated by the brain‒gut axis.
Roti administration attenuated small intestinal injury in Indo-induced model mice. However, Domp administration alone exacerbated this injury. Moreover, Roti mitigated small intestinal injury by increasing Occludin and zonula occludens-1 (ZO-1) expression and decreasing TNF-α and cyclooxygenase 2 (COX-2) expression. However, the effects of Roti were abrogated by Domp. In contrast to Domp, vagotomy before Indo administration did not alter the enteroprotective effects of Roti.
The DA receptor agonist Roti attenuated Indo-induced enteropathy via peripheral DRD2 and could be a potential drug for treating NSAID-mediated enteropathy.
非甾体抗炎药诱导的肠病的特征是上皮屏障和免疫稳态遭到破坏，从而导致诸如充血、溃疡和炎症等症状。研究表明，多巴胺（DA）对胃十二指肠和结肠黏膜具有保护作用。本研究旨在探讨DA对非甾体抗炎药诱导的小肠黏膜损伤的影响。
通过灌胃建立吲哚美辛（Indo，一种常用的非甾体抗炎药）诱导的肠病小鼠模型。将DA激动剂罗替戈汀（Roti）单独或与DA受体2（DRD2）拮抗剂多潘立酮（Domp）联合给予模型小鼠，以确定Roti的作用以及DRD2在该作用中的关键作用。进行双侧迷走神经切断术以确定Roti的作用是否由脑-肠轴介导。
给予Roti可减轻Indo诱导的模型小鼠的小肠损伤。然而，单独给予Domp会加重这种损伤。此外，Roti通过增加闭合蛋白和紧密连接蛋白-1（ZO-1）的表达以及降低肿瘤坏死因子-α（TNF-α）和环氧化酶2（COX-2）的表达来减轻小肠损伤。然而，Domp消除了Roti的作用。与Domp不同，在给予Indo之前进行迷走神经切断术并未改变Roti的肠保护作用。
DA受体激动剂Roti通过外周DRD2减轻Indo诱导的肠病，可能是治疗非甾体抗炎药介导的肠病的潜在药物。
