摘要
目的 通过了解缺氧诱导因子-1α（HIF-1 α）、内皮素-1（ET-1）、肾上腺髓质素（ADM）在缺氧性肺动脉高压（HPH）新生大鼠血清及肺组织中的表达,探讨其在HPH发病中的作用,为防治HPH提供一定的理论依据.方法 将72只新生大鼠随机分为低氧组及常氧组,低氧组建立HPH模型.分别于3、5、7、10、14、21 d测定2组大鼠平均肺动脉压力（mPAP）,并测定血清及肺组织中HIF-1α、ET-1及ADM表达水平；观察肺小动脉形态学变化并测定肺血管重塑指标.结果 1.随缺氧时间延长,新生大鼠mPAP持续增高,与常氧组比较差异有统计学意义（P＜0.05）.2.低氧组大鼠血清HIF-1α及肺组织HIF-1α mRNA在3、5、7、10、14 d均明显高于常氧组,差异均有统计学意义（P均＜0.05）；血清ET-1在各观察时间点均高于常氧组,ET-1 mRNA仅在3、5d时高于常氧组（P＜0.05）；血清ADM于3、5d高于常氧组,而至低氧14、21 d时则明显低于常氧组,ADMmRNA在3、5d时高于常氧组（P＜0.05）.3.低氧7d开始出现肺血管形态及超微结构变化.结论 在HPH的发病机制中,HIF-1 α调控ET-1与ADM,ET-1始终发挥强大的缩血管作用,而ADM仅在早期发挥对血管的保护作用.低氧7d开始出现肺血管重塑.
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.
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2013年第18期1384-1389,共6页
Chinese Journal of Applied Clinical Pediatrics
基金
国家自然科学基金（30960410）
