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一氧化氮在丁酸钠对肠易激综合征小鼠模型结肠收缩抑制作用机制中的作用

Nitric oxide in the mechanisms of inhibitory effects of sodium butyrate on colon contractions in a mouse model of irritable bowel syndrome.

作者信息

Shaidullov Ilnar, Bouchareb Djamila, Sorokina Dina, Sitdikova Guzel

机构信息

Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18, Kremlevskaya Str, 420008, Kazan, Russia.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb;398(2):1905-1914. doi: 10.1007/s00210-024-03403-1. Epub 2024 Aug 28.

DOI:10.1007/s00210-024-03403-1
PMID:39191960
Abstract

Irritable bowel syndrome (IBS) is a multifactorial disorder, with altered intestinal motility, visceral hypersensitivity, and dysfunction of the gut-brain axis. The aim of our study was to analyze the role of nitric oxide (NO) in the inhibitory effects of sodium butyrate on spontaneous contractility of proximal colon in a mouse model of IBS. IBS was induced by intracolonic infusion of acetic acid in the early postnatal period. Spontaneous contractions of proximal colon segments were studied in isometric conditions. The amplitude and frequency of colon contractions were higher in the IBS group. Sodium butyrate exerted inhibitory effects on colon contractions, which were less pronounced in IBS group. NO donors decreased spontaneous colon contractility and prevented the inhibitory effects of sodium butyrate in control and IBS groups. Nitric oxide synthase (NOS) inhibition by L-NAME increased contractile activity more effective in the control group and decreased the inhibitory action of sodium butyrate. In IBS group, preliminary application of L-NAME did not prevent sodium butyrate action. Our data indicate that butyrate exerts its inhibitory effects on colon motility at least partially through activation of NO synthesis. In the IBS model group, the NO-dependent mechanisms were less effective probably due to downregulation of NOS.

摘要

肠易激综合征(IBS)是一种多因素疾病,伴有肠道运动改变、内脏超敏反应和肠-脑轴功能障碍。我们研究的目的是分析一氧化氮(NO)在丁酸钠对IBS小鼠模型近端结肠自发收缩的抑制作用中的作用。在出生后早期通过结肠内注入乙酸诱导IBS。在等长条件下研究近端结肠段的自发收缩。IBS组结肠收缩的幅度和频率更高。丁酸钠对结肠收缩有抑制作用,在IBS组中这种作用不太明显。NO供体降低了结肠的自发收缩性,并消除了丁酸钠在对照组和IBS组中的抑制作用。L-NAME抑制一氧化氮合酶(NOS)在对照组中更有效地增加了收缩活性,并降低了丁酸钠的抑制作用。在IBS组中,预先应用L-NAME并不能阻止丁酸钠的作用。我们的数据表明,丁酸盐至少部分通过激活NO合成对结肠运动产生抑制作用。在IBS模型组中,依赖NO的机制可能由于NOS下调而效果较差。

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本文引用的文献

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