Hypertonicity contributes to seawater aspiration-induced lung injury: Role of hypoxia-inducible factor 1α

ABSTRACT

Drowning is an important public health problem, but the mechanism of acute lung injury induced by near-drowning is rarely reported. The aim of this study is to investigate the role of hypertonicity and HIF-1α in seawater aspiration-induced lung injury. Diverse solutions were used to study the effect of hypertonicity on hypoxia, inflammation, vascular leakage, edema, and HIF-1α expression in lungs of rats. The relationship between hypertonicity and hypoxia, when they induced HIF-1α, was studied and the roles of ATM, PI3K, and p38 in the course of hypertonicity inducing HIF-1α were investigated. At last, our conclusion was verified with HIF-1α inhibitor and inducer in seawater aspiration rats. The results showed that hypertonicity, but not isotonicity and hypotonicity, promoted hypoxia, inflammation, vascular leakage, edema, and HIF-1α expression in lungs. Hypertonicity not only induced HIF-1α in a time- and dose-dependent manner but also could increase HIF-1α synergistically with hypoxia in AEC. Furthermore, hypertonicity increased HIF-1α by promoting its mRNA expression through both ATM and PI3K activation and by suppressing its protein degradation through p38 activation. During hyperosmotic stress, the increased HIF-1α promoted the production of the inflammatory cytokines in NR8383 and elevated monolayer permeability through increasing VEGF in RLMVEC. In conclusion, hypertonicity induced by aspirated seawater aggravated lung injury through increasing HIF-1α which promoted inflammation and edema in lung tissues in rats.

Keywords :

• acute lung injury
• hypoxia-inducible factor 1α
• osmotic pressure
• seawater drowning