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免疫抑制后的胃肠道疾病:一种评估单一疗法对运动参数影响的实验模型。

Gastrointestinal disorders after immunosuppression: an experimental model to evaluate the influence of monotherapy on motility parameters.

作者信息

Dall'Agnol Denize Jussara Rupolo, Corá Luciana Aparecida, Teixeira Maria do Carmo Borges, de Lima Maysa Bruno, Gama Loyane Almeida, Miranda José Ricardo de Arruda, Américo Madileine Francely

机构信息

Postgraduate Program in Pharmacology and Biotechnology - São Paulo State University - UNESP, Institute of Biosciences, Botucatu-SP, Brazil.

Alagoas State University of Health Sciences - UNCISAL, Maceió/AL, Brazil.

出版信息

Exp Physiol. 2017 Aug 1;102(8):924-933. doi: 10.1113/EP086267. Epub 2017 Jul 12.

Abstract

What is the central question of this study? The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. What is main finding and its importance? In our experimental study, immunosuppressive drugs currently in use accelerated gastric emptying whilst increasing the frequency and amplitude of gastric contractions after treatment, except for Mycophenolate and azathioprine. Alternating current biosusceptometry is a useful tool to evaluate side-effects of drugs on the gastrointestinal tract, which will help in understanding the symptoms and improving clinical management of patients. The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. Male Wistar rats were randomly distributed into the following treatment groups: ciclosporin, tacrolimus, prednisone, sirolimus, mycophenolate mofetil, everolimus, azathioprine and control. Each animal was treated for 14 days by gavage with dosages ranging from 1 to 20 mg kg  day considering the area-to-volume ratio and hepatic metabolism. Gastrointestinal transit and gastric contractility measurements were evaluated by alternating current biosusceptometry before and after treatment. Gastric emptying was faster in animals treated with tacrolimus, prednisone, sirolimus and everolimus compared with control animals (126.7 ± 12.7 min). There was a significant increase in the frequency of contractions after ciclosporin, tacrolimus, azathioprine and sirolimus treatment compared with control animals (4.6 ± 0.3 cycles min ). Increases in the amplitude of contraction were observed after treatment with tacrolimus, sirolimus and everolimus compared with control rats (34.9 ± 6.0 dB). The results showed that our animal model was suitable for demonstrating that most immunosuppressive drugs currently in use impaired at least one gastrointestinal motility parameter. As a non-invasive technique, alternating current biosusceptometry is a potentially useful tool for evaluation of side-effects of drugs in gastrointestinal tract, helping us to understand the symptoms to improve clinical management of patients.

摘要

本研究的核心问题是什么?目的是提出一种动物模型,使用非侵入性生物磁技术研究免疫抑制单一疗法对胃肠动力的影响。主要发现及其重要性是什么?在我们的实验研究中,目前使用的免疫抑制药物除霉酚酸酯和硫唑嘌呤外,在治疗后加速了胃排空,同时增加了胃收缩的频率和幅度。交变电流生物药敏测定法是评估药物对胃肠道副作用的有用工具,这将有助于理解症状并改善患者的临床管理。目的是提出一种动物模型,使用非侵入性生物磁技术研究免疫抑制单一疗法对胃肠动力的影响。雄性Wistar大鼠被随机分为以下治疗组:环孢素、他克莫司、泼尼松、西罗莫司、霉酚酸酯、依维莫司、硫唑嘌呤和对照组。考虑到面积与体积比和肝脏代谢,通过灌胃对每只动物进行14天的治疗,剂量范围为1至20mg/kg/天。在治疗前后通过交变电流生物药敏测定法评估胃肠转运和胃收缩性测量。与对照动物相比,用他克莫司、泼尼松、西罗莫司和依维莫司治疗的动物胃排空更快(126.7±12.7分钟)。与对照动物相比,环孢素、他克莫司、硫唑嘌呤和西罗莫司治疗后收缩频率显著增加(4.6±0.3次/分钟)。与对照大鼠相比,用他克莫司、西罗莫司和依维莫司治疗后观察到收缩幅度增加(34.9±6.0dB)。结果表明,我们的动物模型适用于证明目前使用的大多数免疫抑制药物至少损害了一个胃肠动力参数。作为一种非侵入性技术,交变电流生物药敏测定法是评估药物在胃肠道副作用的潜在有用工具,有助于我们理解症状以改善患者的临床管理。

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