一种改良的小鼠气袋模型，用于评估化合物对肉芽肿诱导的软骨降解的影响。

A modified mouse air pouch model for evaluating the effects of compounds on granuloma induced cartilage degradation.

作者信息

Bottomley K M, Griffiths R J, Rising T J, Steward A

机构信息

Department of Drug Discovery, Hoechst Pharmaceutical Research Laboratories, Walton, Milton Keynes.

出版信息

Br J Pharmacol. 1988 Mar;93(3):627-35. doi: 10.1111/j.1476-5381.1988.tb10320.x.

DOI:10.1111/j.1476-5381.1988.tb10320.x

PMID:3370391

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1853833/

Abstract

Employing rat femoral head cartilage implanted in a 6 day old mouse air pouch, the effects of inflammatory stimuli (i.e. cotton pellets, carrageenan, zymosan) on the loss of proteoglycan and collagen and granuloma formation have been studied. 2. Wrapping of the cartilage in cotton resulted in granuloma formation with accelerated loss of proteoglycan and collagen over the 14 day implantation period. The amount of loss increased with increasing weight of cotton. 3. The effects of different classes of anti-rheumatic drugs on granuloma formation and proteoglycan and collagen loss from cotton wrapped femoral head cartilage in the mouse air pouch have been studied. 4. Non-steroidal anti-inflammatory drugs (NSAIDs) had no influence on granuloma formation, but in general accelerated the rates of proteoglycan and collagen loss. 5. Dexamethasone and prednisolone significantly reduced granuloma formation and had a marked protective effect on cartilage breakdown. 6. Of the slow acting anti-rheumatic drugs examined, only gold sodium thiomalate (GSTM) and dapsone significantly decreased cartilage loss, with an accompanying modest decrease in granuloma formation. 7. The immunosuppressants cyclophosphamide and methotrexate, but not azathioprine, reduced cartilage degradation, but had no effect on granuloma formation. 8. The results for the different classes of anti-inflammatory and anti-rheumatic drugs are discussed in relation to their effects in other animal models and their reported therapeutic activities in man. It is concluded that the mouse air pouch method as described offers advantages as an animal model over existing procedures to predict therapeutic efficacy in man.

摘要

通过将大鼠股骨头软骨植入6日龄小鼠气袋中，研究了炎症刺激物（即棉球、角叉菜胶、酵母聚糖）对蛋白聚糖和胶原蛋白损失以及肉芽肿形成的影响。2. 用棉花包裹软骨会导致肉芽肿形成，在14天的植入期内蛋白聚糖和胶原蛋白损失加速。损失量随着棉花重量的增加而增加。3. 研究了不同种类的抗风湿药物对小鼠气袋中用棉花包裹的股骨头软骨肉芽肿形成以及蛋白聚糖和胶原蛋白损失的影响。4. 非甾体抗炎药（NSAIDs）对肉芽肿形成没有影响，但总体上加速了蛋白聚糖和胶原蛋白的损失率。5. 地塞米松和泼尼松龙显著减少了肉芽肿形成，并对软骨破坏有显著的保护作用。6. 在所研究的慢作用抗风湿药物中，只有硫代苹果酸金钠（GSTM）和氨苯砜显著减少了软骨损失，同时肉芽肿形成也有适度减少。7. 免疫抑制剂环磷酰胺和甲氨蝶呤，但硫唑嘌呤没有，减少了软骨降解，但对肉芽肿形成没有影响。8. 讨论了不同种类抗炎和抗风湿药物的结果与它们在其他动物模型中的作用以及在人类中报道的治疗活性的关系。得出的结论是，所描述的小鼠气袋法作为一种动物模型，相对于现有程序在预测人类治疗效果方面具有优势。