Noninvasive Assessment of Bleomycin-Induced Lung Injury and the Effects of Short-Term Glucocorticosteroid Treatment in Rats Using MRI
Noninvasive Assessment of Bleomycin-Induced Lung Injury and the Effects of Short-Term Glucocorticosteroid Treatment in Rats Using MRI
复制标题
DOI：
10.1002/jmri.22476
复制
发表时间：
2011-03-01
影响因子：
4.4
通讯作者：
Beckmann, Nicolau
中科院分区：
文献类型：
--
作者：
Babin, Anna L.;Cannet, Catherine;Beckmann, Nicolau
目的：证明质子 MRI 无创量化博来霉素诱导的损伤的可行性以及糖皮质激素对肺纤维化大鼠模型的影响。材料和方法：Sprague-Dawley 大鼠气管内接受博来霉素，并在损伤发生后第 70 天接受 MRI。一组动物接受布地奈德治疗。结果：博来霉素后前两周的反应以弥散性 MRI 信号为特征，经组织学证实主要与炎症有关。后来，信号增加主要反映了参与纤维化发展的组织重塑，组织学分析表明在检测到 MRI 信号的同一区域有胶原沉积。博来霉素后第 6 天和第 13 天施用布地奈德导致每次皮质类固醇应用 24 小时后 MRI 信号减少。然而，没有观察到完整的信号分辨率。组织学显示布地奈德影响炎症，但不影响纤维化。结论：MRI 无创量化博莱霉素治疗大鼠肺损伤的能力将有助于该肺纤维化模型的体内药理学研究。重复测量开辟了测试化合物的新途径，因为可以轻松比较治疗过程中多个时间点的反应。具体来说，在纤维化已经形成的慢性期进行研究变得可行。
Purpose: To demonstrate the feasibility of proton MRI to noninvasively quantify bleomycin-induced injury and the effects of glucocorticosteroids in a rat model of lung fibrosis.Materials and Methods: Sprague-Dawley rats received bleomycin intra-tracheally and underwent MRI up to day 70 following injury onset. A subgroup of animals was treated with budesonide.Results: The response in the first 2 weeks post-bleomycin, characterized by diffuse MRI signals, was related primarily to inflammation as confirmed by histology. Later, increased signals reflected principally tissue remodeling involved in fibrosis development, as suggested by histological analysis revealing collagen deposition in the same areas where MRI signals had been detected. Budesonide administration at days 6 and 13 after bleomycin resulted in decreased MRI signals 24 h after each corticosteroid application. However, no complete signal resolution was observed. Histology showed that budesonide affected inflammation but not fibrosis.Conclusion: The ability of MRI to noninvasively quantify lung injury in bleomycin-treated rats will facilitate in vivo pharmacological studies in this model of pulmonary fibrosis. Repetitive measurements open new avenues in testing compounds as the responses at several time points during the course of treatment can be easily compared. Specifically, studies at the chronic phase, when fibrosis is already established, become amenable.