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利拉鲁肽(GLP-1 激动剂)在南美栗鼠()听觉爆震伤模型中的应用回顾性分析。

A Retrospective Analysis of Liraglutide (GLP-1 Agonist) Use in a Chinchilla () Model of Auditory Blast Injury.

机构信息

Division of Comparative Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

出版信息

Comp Med. 2024 Jun 1;74(3):179-185. doi: 10.30802/AALAS-CM-23-000077. Epub 2024 Apr 22.

DOI:10.30802/AALAS-CM-23-000077
PMID:38649263
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11267444/
Abstract

Chinchillas are a relatively novel research model compared with other rodent species. They require special considerations when it comes to their husbandry and daily care. Chinchillas tend to be shy animals that are well adapted to masking clinical signs of illness. These characteristics can make them a difficult species to maintain in a research setting. The authors' institution has maintained chinchillas and established standardized daily animal care procedures for them. Chinchillas are most commonly used for auditory research. They are often used to study the mechanism of different induced auditory conditions or injuries as well as exploration for potential alleviating treatments. Often, tested therapeutics have demonstrated potentially beneficial effects but have not been applied in the specific condition or injury of interest. The development of new applications for therapeutics can lead to groundbreaking discoveries, but testing of new therapeutic applications is often initially performed in an animal model without knowing how the therapeutic will behave in the species. During testing, unexpected adverse events may manifest that require more focused monitoring and supportive care. This scenario occurred when adverse effects were observed in a chinchilla blast-injury model after receiving an acylated glucagon-like peptide-1 (GLP-1) receptor agonist. The study involved evaluation of this therapeutic over an extended amount of time after inducing a controlled pressurized blast-injury followed by multiple repeated hearing tests under anesthesia. Chinchillas enrolled in the study exhibited several clinical signs including weight loss, lethargy, labored breathing, neurologic abnormalities, decreased appetite or decreased fecal output, and otitis. Five primary abnormalities were reported on pathology: aspiration pneumonia, hepatic steatosis, right ventricular dilation, pancreatitis, and tubulointerstitial nephritis. Initially abnormal clinical signs, early mortality rates, and pathology were attributed to multiple anesthetic events. However, a retrospective analysis evaluating the association of different study variable exposures in a stratified comparison demonstrated that the early mortality rates were actually associated with the therapeutic drug given for the first time in this species. In this study, we describe the detailed findings of the retrospective analysis and explore different strategies that can be incorporated to maintain good animal welfare and decrease early animal loss.

摘要

相较于其他啮齿类动物,龙猫是一种相对较新的研究模型。在饲养和日常护理方面,它们需要特殊考虑。龙猫通常是害羞的动物,善于掩饰疾病的临床症状。这些特征使得它们在研究环境中难以维持。作者所在机构一直饲养龙猫,并为它们制定了标准化的日常动物护理程序。龙猫最常用于听觉研究。它们常用于研究不同诱导听觉条件或损伤的机制,以及探索潜在的缓解治疗方法。通常,经过测试的治疗方法已证明具有潜在的有益效果,但尚未应用于特定的条件或损伤。新治疗方法的应用可以带来突破性的发现,但在不知道治疗方法在特定物种中表现如何的情况下,通常会首先在动物模型中测试新的治疗应用。在测试过程中,可能会出现意想不到的不良事件,需要更集中的监测和支持性护理。在接受酰化胰高血糖素样肽-1(GLP-1)受体激动剂后,在龙猫爆炸伤模型中观察到不良反应时,就出现了这种情况。该研究涉及在诱导受控加压爆炸伤后,长时间评估这种治疗方法,然后在麻醉下进行多次重复听力测试。参与该研究的龙猫表现出多种临床症状,包括体重减轻、嗜睡、呼吸困难、神经异常、食欲减退或粪便量减少以及耳炎。病理学报告了 5 种主要异常:吸入性肺炎、肝脂肪变性、右心室扩张、胰腺炎和肾小管间质性肾炎。最初的异常临床症状、早期死亡率和病理学归因于多次麻醉事件。然而,对分层比较中不同研究变量暴露的关联进行的回顾性分析表明,早期死亡率实际上与该物种首次使用的治疗药物有关。在这项研究中,我们描述了回顾性分析的详细发现,并探讨了可以采用的不同策略,以维持良好的动物福利并减少早期动物损失。

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