Abstract
Objectives
Reduced levels of long chain-polyunsaturated fatty acids (LCPUFAs) in preterm infants are associated with several neonatal morbidities, including bronchopulmonary dysplasia (BPD). We hypothesized that LCPUFA supplementation would attenuate hyperoxia-induced lung injury in a neonatal mouse model, and we tested our hypothesis in 40%O2-induced-lung injury in neonatal murine model.
Methods
C57BL/6 WT dams were allowed to deliver naturally, and pups were randomized within 12 hours of birth to either hyperoxia (H, 40% O2) or room air (RA) for 10 days. To study the effect of LCPUFAs on hyperoxia-induced lung injury, the pups were randomized to the following groups: 1) RA (vehicle), 2) H (vehicle), 3) H + AA (120mg/kg/day), 4) H + DHA (60mg/kg/day), and 5) H + AA: DHA at 120mg/kg/day and 60mg/kg/day, respectively, maintaining a 2:1 ratio. Mice were gavage fed once daily 50 ul/g body weight from day 1–9. On day 10, the mice were sacrificed, and the lungs were removed for morphometric analyses. Mean Linear Intercept (MLI), Mean Septal Thickness (MST), and Radial Alveolar Count (RAC) were quantified and analyzed using R software and data was shown as mean ± SD.
Results
Compared to RA group, mice in hyperoxia groups showed a significant increase in MLI intercept (RA vs H = 47.75 ± 2.02 vs 56.24 ± 5.54, p < 0.01) and MST (RA vs H = 7.33 ± 0.45 vs 7.88 ± 0.70, p < 0.01), and a significant decrease in RAC (RA vs H = 12.93 ± 0.82 vs 10.26 ± 1, p < 0.01). Compared to H alone, AA: DHA resulted in a significant reduction in hyperoxia-induced MST (H vs H + AA: DHA = 8.70 ± 0.44 vs 6.94 ± 0.74, p < 0.001) and improved hyperoxia-induced reduction in RAC (H vs H + AA: DHA = 9.7 ± 0.9 vs 12.0 ± 1.4, p < 0.001). Noteworthy, while AA decreased hyperoxia-induced MST (H vs H + AA = 8.7 ± 0.4 vs 6.9 ± 0.6, p < 0.001), it significantly increased MLI (H vs H + AA = 58.76 ± 5.9 vs 71.19 ± 6.1, p < 0.001).
Conclusions
We reproduced lung injury in a neonatal murine model using 40% O2 and showed a significant increase in MLI, MST, and decreased RAC. The data also demonstrate that LCPUFAs acts distinctively, and specific fatty acids alone or in combination have contrasting effects. Whether the observed changes are also associated with the inflammatory response needs to be investigated further to better understand the impact of LCPUFAs in hyperoxia-induced lung injury and inflammation.
Funding Sources
Charles H. and Judy H. Family Infant Health Research Program.
A phase II randomized placebo-controlled trial of omega-3 fatty acids for the treatment of acute lung injury*
