Serial Micro-CT Assessment of the Therapeutic Effects of Rosiglitazone in a Bleomycin-Induced Lung Fibrosis Mouse Model

다국어 초록 (Multilingual Abstract)

Objective: The aim of this study was to assess the therapeutic effects of rosiglitazone with serial micro-CT findings before and after rosiglitazone administration in a lung fibrosis mouse model induced with bleomycin.
Materials and Methods: We instilled the bleomycin solution directly into the trachea in twenty mice (female, C57BL/6 mice). After the instillation with bleomycin, mice were closely observed for 3 weeks and then all mice were scanned using micro-CT without sacrifice. At 3 weeks, the mice were treated with rosiglitazone on days 21 to 27 if they had abnormal CT findings (n = 9, 45%). For the mice treated with rosiglitazone, we performed micro-CT with mouse sacrifice 2 weeks after the rosiglitazone treatment completion. We assessed the abnormal CT findings (ground glass attenuation, consolidation, bronchiectasis, reticular opacity, and honeycombing) using a five-point scale at 3 and 6 weeks using Wilcoxon-signed ranked test. The micro-CT findings were correlated with the histopathologic results.
Results: One out of nine (11.1%) mice improved completely. In terms of consolidation, all mice (100%) showed marked decrease from 3.1 ± 1.4 at 3 weeks to 0.9 ± 0.9 at 6 weeks (p = 0.006). At 6 weeks, mild bronchiectasis (n = 6, 66.7%), mild reticular opacity (n = 7, 77.8%) and mild honeycomb patterns (n = 3, 33.3%) appeared.
Conclusion: A serial micro-CT enables the evaluation of drug effects in a lung fibrosis mouse model.

참고문헌 (Reference)

1 Lakatos HF, "The Role of PPARs in Lung Fibrosis" 2007 : 71323-, 2007

2 Aono Y, "Surfactant protein-D regulates effector cell function and fibrotic lung remodeling in response to bleomycin injury" 185 : 525-536, 2012

3 Lee HJ, "Semiquantitative measurement of murine bleomycin-induced lung fibrosis in in vivo and postmortem conditions using microcomputed tomography: correlation with pathologic scores--initial results" 43 : 453-460, 2008

4 Burgess HA, "PPARgamma agonists inhibit TGF-beta induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis" 288 : L1146-L1153, 2005

5 Ford NL, "Optimization of a retrospective technique for respiratory-gated high speed micro-CT of free-breathing rodents" 52 : 5749-5769, 2007

6 Ritman EL, "Micro-computed tomography-current status and developments" 6 : 185-208, 2004

7 Yamashita CM, "Matrix metalloproteinase 3 is a mediator of pulmonary fibrosis" 179 : 1733-1745, 2011

8 Johnson KA, "Imaging techniques for small animal imaging models of pulmonary disease: micro-CT" 35 : 59-64, 2007

9 Jin GY, "Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: assessed by micro-computed tomography and pathologic scores" 81 : 1901-1906, 2012

10 Genovese T, "Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury" 25 : 225-234, 2005

11 이재아, "Bleomycin 유도 폐 섬유화 쥐 모델에서 미세 전산화단층촬영의 유용성" 대한결핵및호흡기학회 67 (67): 436-444, 2009

12 Peikert T, "Assessment of current practice in the diagnosis and therapy of idiopathic pulmonary fibrosis" 102 : 1342-1348, 2008

13 Raghu G, "An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management" 183 : 788-824, 2011

14 Langheinrich AC, "Acute rat lung injury: feasibility of assessment with micro-CT" 233 : 165-171, 2004