Changes and significance of endothelin-1 in lung tissue of hypoxic pulmonary hypertension development in neonatal rats / 中华实用儿科临床杂志

ABSTRACT

Objective To know about the effect and significance of endothelin-1 (ET-1) in pathogenesis of hypoxic pulmonary hypertension(HPH) in neonatal rats.Methods The 120 newborn Wistar rats were randomly divided into hypoxic group and control group,and the rats of hypoxic group were made into HPH model.Mean pulmonary arterial pressure(mPAP) was measured on day 3,5,7,10,14 and 21 after hypoxia.The morphological change of pulmonary vessels were observed,and pulmonary vascular remodeling indexes were also obtained,including the ratio of middle wall thickness to external diameter of small pulmonary arteries (MT％) and the ratio of media cross-section area to total cross-sectional area of small pulmonary arteries(MA％).Immunohistochemistry and Western blot tests were done to determine the expression of ET-1 in lung tissue.Results 1.After hypoxia for 3,5,7,10,14,21 days,the levels of mPAP in hypoxia group[(8.492 ± 1.548) mm Hg,(10.022 ± 1.182) mm Hg,(11.470 ± 2.868) mm Hg,(16.842 ±2.154) mm Hg,(12.824 ± 2.859) mm Hg,(21.036 ± 2.590) mm Hg; 1 mm Hg =0.133 kPa] were significantly higher than those in control group[(5.141 ± 1.022) mm Hg,(8.137 ± 1.057) mm Hg,(8.730 ±0.868) mm Hg,(12.125 ±2.541) mm Hg,(8.920 ±0.744) mm Hg,(11.156 ±1.644) mm Hg] (all P ＜0.05).2.Seven days after hypoxia exposure,small pulmonary arterials remodeling was observed.MT％ [(53 ± 11) ％] and MA％ [(60 ± 9) ％]in hypoxia group were also significantly higher than those in control group [(49 ± 11) ％,(54 ± 8) ％] (all P ＜ 0.05).3.The results of immunohistochemistrythe expression intensities of ET-1 were significantly higher in hypoxia group (0.614,0.613,0.651) after hypoxia for 3,5,7 days than those in control group (0.433,0.386,0.369) (all P ＜ 0.05).4.The results of Western blotthe levels of ET-1 were significantly higher in hypoxia group(4.885 ± 1.391,4.434 ± 1.726,6.309 ± 0.330,2.353 ± 0.961) after hypoxia for 3,5,7 and 10 days than those in control group (1.698 ± 0.794,1.454 ± 0.776,2.045 ± 0.668,0.766 ± 0.515) (all P ＜ 0.05).5.The results of correlation analysis:the total expression of ET-1 protein was positively correlated with the total level of mPAP on 3-7 days after hypoxia (r =0.459,P ＜ 0.05).However,the expression of ET-1 had no significant correlation with MT％ and MA％ (rMT =-0.041,rMA =0.322,all P ＞ 0.05).Conclusions The level of ET-1 in lung tissue of HPH newborn rats increased in the early stage after hypoxia exposure and no longer increased during the late stage,which indicated that hypoxia tolerance prevailed.ET-1 acted as an early reactive marker in the process of HPH development in neonatal rats and may be mainly associated with elevated mPAP,which further prompted that through valid means to inhibit the expression of ET-1 in the early stage of hypoxia,in which the prevention and treatment of this disease may be more effective.