Novel sequential stress model for functional dyspepsia: Efficacy of the herbal preparation STW5

Novel sequential stress model for functional dyspepsia: Efficacy of the herbal preparation STW5
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DOI:
10.1016/j.phymed.2015.03.012
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发表时间:
2015-05-15
期刊:
影响因子:
7.9
通讯作者:
Khayyal, Mohamed T.
Khayyal, Mohamed T.
中科院分区:
医学1区
文献类型:
--
作者:
Abdel-Aziz, Heba;Wadie, Walaa;Khayyal, Mohamed T.

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工作背景:功能性消化不良(FD)的潜在有用的药物的许多筛选程序依赖于动物暴露于压力的早期生活(新生儿母亲分离,NMS)或在成年期(约束应力,RS)。目的:由于许多临床病例FD已与压力在早期生活中,随后在成年期的压力,一个连续的模型模拟的临床情况进行了描述。为了探索该模型的有效性,STW 5,一种多组分的草药制剂,在FD中被证明是有用的,进行了测试。研究设计/方法:建立一个连续的压力模型,大鼠出生后暴露于NMS,随后在成年RS。测量血浆中的应激激素和生长激素释放肽,同时评估胃底条对平滑肌兴奋剂和松弛剂的反应性。STW 5的治疗前几天和暴露期间RS在预防应激模型引起的变化的有效性的报告和比较,它的疗效时,在动物中使用RS单独。结果:反应的刺激剂和松弛剂在不同程度上减少在研究的模型,但与STW 5的治疗往往正常化胃的反应。生长素释放肽、皮质酮释放因子和皮质酮的血浆水平均被RS和序贯模型所升高。STW 5治疗倾向于防止精神错乱的parameters.Conclusion:序贯应力模型在药物筛选中具有潜在的实用性,因为它模拟了更多的临床环境。此外,研究结果进一步阐明了STW 5在FD中的作用机制。(C)2015作者由爱思唯尔有限公司出版。
Background: Many screening procedures for agents with potential usefulness in functional dyspepsia (FD) rely on animals exposed to stress early in life (neonatal maternal separation, NMS) or in adulthood (restraint stress, RS).Purpose: Since many clinical cases of FD have been associated with stress in early life followed by stress in adulthood, a sequential model simulating the clinical situation is described. To explore the validity of the model, the efficacy of STW5, a multicomponent herbal preparation of proven usefulness in FD, was tested.Study design/methods: A sequential stress model established where rats are exposed to NMS after birth followed later by RS in adulthood. Stress hormones and ghrelin were measured in plasma, while responsiveness of stomach fundus strips to smooth muscle stimulants and relaxants was assessed ox viva. The effectiveness of treatment with STW5 a few days before and during exposure to RS in preventing changes induced by the stress model is reported and compared to its efficacy when used in animals subjected to RS alone.Results: Responses to both stimulants and relaxants were reduced to various extents in the studied models, but treatment with STW5 tended to normalize gastric responsiveness. Plasma levels of ghrelin, corticosterone releasing factor, and corticosterone were raised by RS as well as the sequential model. Treatment with STW5 tended to prevent the deranged parameters.Conclusion: The sequential stress model has a place in drug screening for potential usefulness in FD as it simulates more the clinical setting. Furthermore, the findings shed more light on the mechanisms of action of STW5 in FD. (C) 2015 The Authors. Published by Elsevier GmbH.