Tetrandrine attenuates hyperoxia-induced lung injury in newborn rats via NF-κB p65 and ERK1/2 pathway inhibition.

BACKGROUND

Bronchopulmonary dysplasia (BPD) is an important cause of respiratory illness in preterm newborns that results in significant morbidity and mortality. Hyperoxia is a critical factor in the pathogenesis of BPD, hyperoxia-induced lung injury model has similar pathological manifestations as human BPD. Tetrandrine (Tet) is known to suppress oxidative stress, apoptosis and inflammation. Thus it has been used to prevent organ injuries. However, the protective effect of Tet against hyperoxia-induced lung injury in newborn rats has not been reported.

METHODS

A hyperoxia-induced lung injury model was established using newborn rats exposed to high O levels. The models were treated with various concentrations of Tet, and a lung function test was conducted. Then, the lung tissues and blood were collected to detect the effect of Tet on cell apoptosis, inflammatory response, and fibrosis. The effect of Tet on nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase1/2 (ERK1/2) pathways was also determined.

RESULTS

Lung function was decreased in hyperoxia-induced rats, and Tet could reverse this inhibiting effect. For oxidative stress, Tet caused an increase in the levels of antioxidant enzymes. The apoptosis rate and apoptosis-related proteins were decreased in hyperoxia-induced rats after Tet treatment. Additionally, Tet treatment could reduce inflammatory factor levels, while increasing CD4IFN-γ T cell levels and decreasing CD4IL-4 T cell levels. Tet treatment was also able to inhibit the expression of fibrosis-related markers and NF-κB and ERK1/2 pathways.

CONCLUSIONS

Tet demonstrated potent activity against hyperoxia-induced lung injury in newborn rats through NF-κB and ERK1/2 pathway inhibition.