Rosiglitazone, a Peroxisome Proliferator-Activated Receptor-gamma Agonist, Restores Alveolar and Pulmonary Vascular Development in a Rat Model of Bronchopulmonary Dysplasia.
- Author:
Hyun Ju LEE
1
;
Youn Jin LEE
;
Chang Won CHOI
;
Jin A LEE
;
Ee Kyung KIM
;
Han Suk KIM
;
Beyong Il KIM
;
Jung Hwan CHOI
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: Bronchopulmonary dysplasia; peroxisome proliferator-activated receptor-gamma; rosiglitazone; alveolarization
- MeSH: Animals; Bronchopulmonary Dysplasia/*drug therapy; Female; Hypertension, Pulmonary/drug therapy; Immunohistochemistry; Lung/drug effects/pathology; PPAR gamma/*agonists; Rats; Rats, Sprague-Dawley; Thiazolidinediones/*therapeutic use; Vasodilator Agents/*therapeutic use
- From:Yonsei Medical Journal 2014;55(1):99-106
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: We tested whether rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-gamma agonist, can restore alveolar development and vascular growth in a rat model of bronchopulmonary dysplasia (BPD). MATERIALS AND METHODS: A rat model of BPD was induced through intra-amniotic delivery of lipopolysaccharide (LPS) and postnatal hyperoxia (80% for 7 days). RGZ (3 mg/kg/d, i.p.) or vehicle was given daily to rat pups for 14 days. This model included four experimental groups: No BPD+vehicle (V), No BPD+RGZ, BPD+V, and BPD+RGZ. On D14, alveolarization, lung vascular density, and right ventricular hypertrophy (RVH) were evaluated. RESULTS: Morphometric analysis revealed that the BPD+RGZ group had significantly smaller and more complex airspaces and larger alveolar surface area than the BPD+V group. The BPD+RGZ group had significantly greater pulmonary vascular density than the BPD+V group. Western blot analysis revealed that significantly decreased levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 by the combined exposure to intra-amniotic LPS and postnatal hyperoxia were restored by the RGZ treatment. RVH was significantly lesser in the BPD+RGZ group than in the BPD+V group. CONCLUSION: These results suggest that RGZ can restore alveolar and pulmonary vascular development and lessen pulmonary hypertension in a rat model of BPD.
