缺氧诱导因子1α及其调控因子在新生大鼠缺氧性肺动脉高压发病机制中作用的研究  

Effect of hypoxia-inducible factor-1α, endothelin-1 and inducible nitric oxide synthase in the pathogenesis of hypoxia-induced pulmonary hypertension of the neonatal rats

作　　者：桑葵[1,2] 周英[1] 李明霞[1] 

机构地区：[1]新疆医科大学第一附属医院新生儿科,乌鲁木齐830054 [2]香港大学深圳医院儿科,深圳518053

出　　处：《中华儿科杂志》2012年第12期919-924,共6页Chinese Journal of Pediatrics

基　　金：国家自然科学基金资助项目（30960410）

摘　　要：目的通过了解缺氧诱导因子1α（hypoxia inducible factor-1 alpha，HIF-1α）及其调控因子：内皮素-1（endothelin-1，ET-1）、诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）在新生大鼠缺氧性肺动脉高压（hypoxia induced pulmonary hypertension，HPH）血清及肺组织中的表达，探讨HIF-1α在新生大鼠HPH发病机制中的作用。方法建立新生大鼠HPH模型：将120只新生Wistar大鼠依照随机数字表法分为低氧组和正常对照组，分别于缺氧3、5、7、10、14、21d取低氧组及同日龄对照组新生大鼠各10只测定其平均肺动脉压（mean pulmonary arteria pressure，mPAP）、血清HIF-1α、iNOS、ET-1含量，及肺组织上述基因mRNA的表达水平。结果（1）缺氧3、5、7、10、14、21d，低氧组新生大鼠mPAP检测值分别为：[8．47±1．45，10．04±1．69，10．89±2．97，16．96±1．97，13．01±1．93，21．04±2．13（mmHg）（1mmHg=0．133kPa）]，较对照组检测值：[5．11±1．06，8．12±1．11，8．77±0．92，12．23±1．78，8．89±0．89，11．09±1．64（mmHg）]显著增高，差异有统计学意义（P〈0．05）；（2）低氧组新生大鼠血清HIF-1α含量在缺氧3、5、7、10、14d检测值分别为：[0．83±0．07，0．84±0．17，0．97±0．13，1．10±0．30，0．92±0．19（pg/nm01）]，明显高于对照组检测值：[0．26±0．20，0．37±0．16，0．44±0．18，0．41±0．23，0．66±0．18（pg／nmol）]，差异有统计学意义（P〈0．05）；肺组织HIF-1αmRNA表达在缺氧3、5、7d检测值为：1．301±0．47，1．032±0．47，1．453±0．76，明显高于对照组检测值：0．231±0．26，0．425±0．59，0．692±0．13，差异有统计学意义（P〈0．05）。血清ET-1含量在缺氧3、5、7、10、14、21d检测值分别为：[51．50±3．19，44．1±10．81，56．85±9．10，52．91±9．59，51．16±8．87，50．21±10．41（pg／nm01）]，均明显高于对照组检测值Objective To study the effect of hypoxia-inducible factor-1α （HIF-lcL） in the pathogenesis of hypoxia-indueed pulmonary hypertension （ HPH ） of the neonatal rats through the study on the expression level of HIF-1αand its regulation factors： endothelin-1 （ET-1） and inducible nitric oxide synthase （iNOS） in blood serum and lung tissue. Methods To make an HPH model of neonatal rats, 120 newborn Wistar rats were divided at random into two groups： HPH group and the regular oxygen controlled group with the same birthday. The rats of the two groups were put in the condition of hypoxia for 3, 5, 7, 10, 14,21 days and then 10 rats of HPH group and control group were picked up, their mean pulmonary arterial pressure （mPAP） , serum HIF-1α, and iNOS, and ET-1 content were tested, and finally their lung tissue was taken after they were sacrificed and the expression level of the gene mRNA of HIF-1α, iNOS and ET-1. Results （ 1 ） The rats experienced hypoxia for 3, 5,7, 10, 14 or 21 days had an increasing mPAP： [ 8.47 ± 1.45,10.04 ± 1.69,10. 89 ± 2. 97,16. 96 ± 1.97,13.01 ± 1.93, 21.04 ± 2. 13 （mm Hg） ], which had a significant differences compared with control groups[ 5.11 ± 1.06,8. 12 ± 1.11,8.77 ±0. 92,12. 23 ± 1.78,8. 89 ± 0. 89,11.09 ± 1.64 （ mm Hg） ] （P 〈 0.05）. （2） The rats in hypoxia group had a higher serum HIF-1α[0. 83 ±0.07,0.84 ±0. 17,0.97 ±0. 13,1.10 ±0.30,0.92 ±0. 19 （pg/nmol） ] than the control group [0.26 ±0.20,0.37 ±0.16,0.44 ±0.18,0.41 ± 0. 23 , 0. 66 ± 0.18 （ pg/nmol ） ] as they experienced hypoxia for 3, 5, 7, 10, and 14 days （P 〈0. 05） ; HIF-1α mRNA expression in lung tissue （ 1. 301 ± 0.47,1. 032 ± 0. 47,1. 453 ± 0.76 ） was also significantly higher than that of the control group （0.231 ±0.26,0.425 ±0.59,0.692 ±0.13） （P〈0.05）; serum ET-1 levels [51.50±3.19,44.1 ± 10. 81,56. 85 ± 9. 10, 52. 91 ± 9.59,51.16 ± 8. 87, 50. 21 ± 10.41 （pg/nmol） ] were clearly higher than that of the control gro

关 键 词：缺氧诱导因子1Α 缩血管肽类1 一氧化氮合酶 高血压 肺性 大鼠 

分 类 号：R722.1[医药卫生—儿科]