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三种用于模拟应激相关黏膜疾病病理生理学的急性应激模型的比较

Comparison of three acute stress models for simulating the pathophysiology of stress-related mucosal disease.

作者信息

Saxena Bhagawati, Singh Sanjay

机构信息

Department of Pharmacology, L. J. Institute of Pharmacy.

Division of Pharmacology and Toxicology, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University).

出版信息

Drug Discov Ther. 2017 May 30;11(2):98-103. doi: 10.5582/ddt.2016.01081. Epub 2017 Mar 19.

Abstract

Stress-related mucosal disease (SRMD) is highly prevalent in intensive care patients leading to increasing treatment cost and mortality. SRMD is a disease elusive of ideal treatment. Evaluation of drugs is very pertinent for the efficient and safe treatment of SRMD. It relies mainly on in vivo screening models. There are various stress models, and till date, none of them is validated for simulating the SRMD pathophysiology. The present study aims to choose the best model, which reproduce pathophysiology of SRMD, among previously established stress models. This study evaluates ulcer index, hexosamine content, microvascular permeability, and gastric content in three acute stress models (cold-restraint, restraint, and water immersion restraint). Macroscopic pictures of the ulcerogenic stomach explain that in contrast to other models, cold-restraint stress (CRS) exposure produced marked ulcers on the fundic area of the stomach. Results of the present study depicted that each stress model significantly increased ulcer index, microvascular permeability and decreased hexosamine level, however, the maximum in the case of CRS-exposed rats. Total acidity and pH of the gastric content remains unchanged in all the stress models. On the contrary, the gastric volume significantly decreased only in case of CRS, while unchanged in other stress models. The overall results revealed that the CRS resembles the pathophysiology of SRMD closely. It is the best and feasible model among all the models to evaluate drugs for the treatment of SRMD.

摘要

应激相关黏膜病(SRMD)在重症监护患者中高度流行,导致治疗成本和死亡率不断上升。SRMD是一种难以找到理想治疗方法的疾病。药物评估对于SRMD的有效和安全治疗非常重要。它主要依赖于体内筛选模型。有多种应激模型,但迄今为止,没有一种模型经过验证可模拟SRMD的病理生理学。本研究旨在从先前建立的应激模型中选择能够重现SRMD病理生理学的最佳模型。本研究评估了三种急性应激模型(冷束缚、束缚和水浸束缚)中的溃疡指数、氨基己糖含量、微血管通透性和胃内容物。致溃疡胃的宏观图像表明,与其他模型相比,冷束缚应激(CRS)暴露在胃底区域产生了明显的溃疡。本研究结果表明,每种应激模型均显著增加溃疡指数、微血管通透性并降低氨基己糖水平,然而,CRS暴露大鼠的变化最为明显。所有应激模型中胃内容物的总酸度和pH值均保持不变。相反,仅CRS组胃体积显著减小,而其他应激模型中胃体积不变。总体结果表明,CRS与SRMD的病理生理学非常相似。它是所有模型中评估治疗SRMD药物的最佳且可行的模型。

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