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在大鼠化疗诱导的粘膜炎短期模型中,利用自发掘洞行为评估总体健康状况。

The assessment of general well-being using spontaneous burrowing behaviour in a short-term model of chemotherapy-induced mucositis in the rat.

作者信息

Whittaker A L, Lymn K A, Nicholson A, Howarth G S

机构信息

School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy Campus, South Australia, Australia

School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy Campus, South Australia, Australia.

出版信息

Lab Anim. 2015 Jan;49(1):30-9. doi: 10.1177/0023677214546913. Epub 2014 Aug 11.

Abstract

Mucositis is a common and serious side-effect experienced by cancer patients during treatment with chemotherapeutic agents. Consequently, programmes of research focus on the elucidation of novel therapeutics for alleviation of mucositis symptoms, and these frequently use animal models. However, although these models are assumed to be painful and distressing to the animal, endpoints are difficult to determine. The aim of this study was to evaluate whether a change in burrowing behaviour could provide an indication of disease onset and potentially be applied as a humane endpoint. Baseline burrowing behaviour was measured in healthy animals on three occasions by determining the weight of gravel displaced from a hollow tube. Mucositis was then induced in the same animals by intraperitoneal injection of 5-fluorouracil (150 mg/kg) and burrowing behaviour recorded over three consecutive days. Standard measures of disease progression, including body weight loss and clinical score, were also made. The presence of mucositis was confirmed at necropsy by findings of decreased duodenal and colon lengths, and reduced liver, spleen and thymus weights in comparison with non-treated control animals. Histological score of the jejunum and ileum was also significantly increased. Mucositis onset coincided with a decrease in mean burrowing behaviour which was progressive, however this result did not achieve statistical significance (P = 0.66).We conclude that burrowing may be a useful indicator of inflammation in the mucositis model, although this requires further characterization. Pre-selection of animals into treatment groups based on their prior burrowing performance should be pursued in further studies.

摘要

黏膜炎是癌症患者在接受化疗药物治疗期间常见且严重的副作用。因此,研究项目聚焦于阐明缓解黏膜炎症状的新型疗法,并且这些研究经常使用动物模型。然而,尽管这些模型被认为会给动物带来疼痛和痛苦,但终点却难以确定。本研究的目的是评估掘洞行为的变化是否能指示疾病的发生,并有可能作为一个人道终点来应用。通过测定从空心管中排出的砾石重量,在三个不同时间点对健康动物的基线掘洞行为进行了测量。然后通过腹腔注射5-氟尿嘧啶(150mg/kg)在同一批动物中诱发黏膜炎,并连续三天记录掘洞行为。还对疾病进展的标准指标,包括体重减轻和临床评分进行了测定。与未治疗的对照动物相比,尸检时发现十二指肠和结肠长度缩短,肝脏、脾脏和胸腺重量减轻,从而证实了黏膜炎的存在。空肠和回肠的组织学评分也显著升高。黏膜炎的发作与平均掘洞行为的下降同时出现,且这种下降是渐进性的,然而这一结果未达到统计学显著性(P = 0.66)。我们得出结论,掘洞行为可能是黏膜炎模型中炎症的一个有用指标,尽管这还需要进一步的特征描述。在进一步的研究中,应根据动物先前的掘洞表现对其进行预先分组。

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