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复方药物 Spascupreel 可减轻大鼠应激相关的肠道功能障碍。

The multicomponent medication Spascupreel attenuates stress-induced gut dysfunction in rats.

机构信息

INRA, ToxAlim, UMR 1331, Neuro-Gastroenterology and Nutrition Group, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France.

Heel GmbH, Baden-Baden, Germany.

出版信息

Neurogastroenterol Motil. 2020 May;32(5):e13798. doi: 10.1111/nmo.13798. Epub 2020 Feb 14.

Abstract

BACKGROUND

Irritable bowel syndrome (IBS) is a common disorder worldwide. It is characterized by abdominal pain/discomfort and changes in bowel habits. Due to the multifactorial pathophysiology and the heterogeneity of IBS patients, appropriate treatment of IBS is still a challenge. Spascupreel (SP-11), as a multicomponent medication, has the potential to modulate multiple pathophysiological pathways simultaneously. Therefore, the objective of the current study was to investigate the effects of oral SP-11 treatment on stress-induced changes of peripheral and central functions in a rat model mimicking human IBS.

METHODS

Naïve Wistar rats were treated with SP-11 (0.9 tab/kg) or NaCl 0.9% by oral gavage for 4 days before 2-hour partial restraint stress (PRS) procedure. Twenty minutes after PRS, central and peripheral stress-induced changes affecting IBS were assessed. These include the hypothalamic-pituitary-adrenal (HPA) axis response through plasma ACTH and corticosterone measurements, visceral pain in response to colorectal distension, gut permeability, colonic mast cell number, and sensitization as well as gut transit time.

RESULTS

Treatment with SP-11 reduced the HPA axis activation in response to PRS. At the gut level, a reduction in colonic hypersensitivity to colorectal distension, a normalization of gut transit time acceleration, a reduced mast cell sensitization, and a trend toward reduced gut hyperpermeability were observed.

CONCLUSIONS

These data suggest that stress-induced IBS signs can be reduced using SP-11 in rats. The observed effects and the good tolerability of the drug make SP-11 an innovative candidate in the management of IBS.

摘要

背景

肠易激综合征(IBS)是一种常见的全球疾病。其特征为腹痛/不适和肠习惯改变。由于多因素病理生理学和 IBS 患者的异质性,IBS 的适当治疗仍然是一个挑战。Spascupreel(SP-11)作为一种多组分药物,具有同时调节多种病理生理途径的潜力。因此,本研究的目的是研究口服 SP-11 治疗对模拟人类 IBS 的大鼠模型中外周和中枢功能应激诱导变化的影响。

方法

在 2 小时部分束缚应激(PRS)程序之前,用 SP-11(0.9 片/公斤)或 0.9%NaCl 通过口服灌胃处理 4 天,对 Wistar 大鼠进行预处理。在 PRS 后 20 分钟,评估影响 IBS 的中枢和外周应激诱导变化。这些变化包括通过血浆 ACTH 和皮质酮测量评估下丘脑-垂体-肾上腺(HPA)轴反应、对结肠扩张的内脏疼痛、肠道通透性、结肠肥大细胞数量和敏化以及肠道转运时间。

结果

SP-11 治疗可减轻 PRS 对 HPA 轴的激活。在肠道水平,观察到结肠对结肠扩张的超敏反应降低,肠道转运时间加速正常化,肥大细胞敏化降低,肠道通透性增加趋势降低。

结论

这些数据表明,在大鼠中使用 SP-11 可减轻应激诱导的 IBS 体征。观察到的作用和药物的良好耐受性使 SP-11 成为 IBS 管理的创新候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f47/7217055/8e4868ff936c/NMO-32-e13798-g001.jpg

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