Changes of hypoxia-inducible factor-1α, endothelin-1 and adrenomedullin in newborn rats with hypoxia-induced pulmonary hypertension / 中华实用儿科临床杂志

ABSTRACT

Objective To provide the foundation of theory on prevention of hypoxia-induced pulmonary hypertension (HPH) by investigating the concentrations in the serum and expression levels in the lung tissue,and by studying the roles of hypoxia-inducible factor-1 α (HIF-1 α),endothelin-1 (ET-1) and adrenomedullin (ADM) in newborn rats with HPH.Methods Seventy-two newborn rats were randomly divided into hypoxic group(hypoxia exposure) and normoxic group.The mean pulmonary arteria pressure (mPAP),concentrations in the serum and expression levels in the lung tissue of the above-mentioned factors were measured in these neonatal rats after 3,5,7,10,14 and 21 days,including hypoxic group and normoxic group,respectively.The morphology of pulmonary arterioles was observed and the vascular remodeling indexes were measured.Results 1.Compared with the normoxic group,the mPAP increased with the prolonged hypoxic time in the hypoxic group(P ＜ 0.05).2.Concentrations in the serum and expression levels in the lung tissue of HIF-1 α were higher than those of the normoxic group on 3,5,7,10,14 days (all P ＜ 0.05).The serum concentration of ET-1 elevated significantly in the hypoxic group at each time point,and ET-1 mRNA increased only on 3 and 5 days of the hypoxia group.The serum concentration of ADM level in the hypoxic group was higher than that of the normoxic group on 3 and 5 days,but lower than the normoxic group after 14 and 21 days of hypoxia,and the expression of ADM mRNA in the lung tissue was higher on 3 and 5 days in the hypoxic group.3.Morphology and ultrastructure of the pulmonary arteries change were found after 7 days of hypoxia exposure.Conclusions HIF-1α may regulate ET-1 and ADM in the pathogenesis of HPH.ET-1 plays a powerful role by pulmonary vasoconstriction and vascular remodeling,whereas ADM displays the protective effects on blood vessels in the early stages of HPH.Pulmonary vascular remodeling occurs in the hypoxic group after 7 days of hypoxia.