Aerosolized PPARγ agonist Pioglitazone + Synthetic Surfactant Protein B Mimic B-YL Prevents Hyperoxia-induced Neonatal Lung Injury in Rats

Abstract

Background

Despite improvements in perinatal care, Bronchopulmonary Dysplasia (BPD) in extremely premature infants has not decreased. Postnatal surfactant therapy provides symptomatic relief from Respiratory Distress Syndrome, but it does not translate into a reduction in BPD. Therefore, the search for effective interventions to prevent BPD continues.

Objectives

Since PPARγ agonists have been demonstrated to promote neonatal lung maturation and injury repair, we hypothesized that a combined PPARγ agonist [pioglitazone (PGZ)] and synthetic lung surfactant [surfactant protein B (SP-B) mimic B-YL] formulation would stimulate lung maturation and block hyperoxia-induced neonatal lung injury more effectively than either modality alone.

Methods

One-day old Sprague-Dawley rat pups were administered PGZ+B-YL via nebulization every 24h up to 72h. The pups were exposed to either 21% or 95% O ₂, following which pups were sacrificed and lungs examined for markers of lung maturation [(PPARγ, SP-C, and cholinephosphate cytidylyltransferase (CCT-α) by Western analysis), and (H ³)triolein uptake] and injury repair (bronchoalveolar lavage cell count and protein content; LEF-1, Fibronectin, ALK5, and β-catenin protein levels by Western analysis].

Results

The markers of alveolar epithelial-mesenchymal maturation (SP-C, CCT-α, and triolein uptake) increased significantly in the PGZ+B-YL group, more than with either drug alone. Similarly, markers of hyperoxia-induced lung injury were blocked effectively with PGZ+B-YL treatment.

Conclusions

Nebulized PPARγ agonist PGZ with synthetic lung surfactant accelerates lung maturation and prevents neonatal hyperoxia-induced lung injury more than with either modality alone, potentially preventing BPD more effectively.