Tigani Bruno, Schaeublin Elisabeth, Sugar Rosemary, Jackson Alan D, Fozard John R, Beckmann Nicolau
Central Technologies, Novartis Pharma AG, Lichtstrasse 35, CH-4002 Basel, Switzerland.
Biochem Biophys Res Commun. 2002 Mar 22;292(1):216-21. doi: 10.1006/bbrc.2002.6633.
A detailed analysis has been carried out of the correlation between the signals detected by MRI in the rat lung after allergen or endotoxin challenge and parameters of inflammation determined in the broncho-alveolar lavage (BAL) fluid. MRI signals after allergen correlated highly significantly with the BAL fluid eosinophil number, eosinophil peroxidase activity and protein concentration. Similar highly significant correlations were seen when the anti-inflammatory glucocorticosteroid, budesonide, manifested against allergen. In contrast, following endotoxin challenge, mucus was the sole BAL fluid parameter that correlated significantly with the long lasting signal detected by MRI. Since edema is an integral component of pulmonary inflammation, MRI provides a noninvasive means of monitoring the course of the inflammatory response and should prove invaluable in profiling anti-inflammatory drugs in vivo. Further, the prospect of noninvasively detecting a sustained mucus hypersecretory phenotype in the lung brings an important new perspective to models of chronic obstructive pulmonary diseases.
对大鼠肺部在过敏原或内毒素激发后通过MRI检测到的信号与支气管肺泡灌洗(BAL)液中确定的炎症参数之间的相关性进行了详细分析。过敏原激发后的MRI信号与BAL液中的嗜酸性粒细胞数量、嗜酸性粒细胞过氧化物酶活性和蛋白质浓度高度显著相关。当抗炎糖皮质激素布地奈德对抗过敏原时,也观察到了类似的高度显著相关性。相比之下,在内毒素激发后,黏液是唯一与MRI检测到的持久信号显著相关的BAL液参数。由于水肿是肺部炎症的一个组成部分,MRI提供了一种监测炎症反应过程的非侵入性方法,并且在体内分析抗炎药物方面应被证明具有极高价值。此外,在肺部无创检测持续的黏液高分泌表型的前景为慢性阻塞性肺疾病模型带来了一个重要的新视角。