HIF-1α、ET-1和ADM在低压低氧性肺动脉高压大鼠肺血管的表达及意义  

The expression and significance of HIF-1α,ET-1 and ADM in lung vessel of rats with hypobaric hypoxic-induced pulmonary hypertension

作　　者：徐娇阳 是文辉[3] 付勇[4] 李建瑛[3] 刘江伟[3] 桂俊豪[2] 余伍忠[1,2] 

机构地区：[1]石河子大学医学院 [2]兰州军区乌鲁木齐总医院临床医学研究所,新疆乌鲁木齐830000 [3]兰州军区乌鲁木齐总医院动物实验科,新疆乌鲁木齐830000 [4]兰州军区乌鲁木齐总医院病理科,新疆乌鲁木齐830000

出　　处：《中国实验诊断学》2015年第12期1996-2000,共5页Chinese Journal of Laboratory Diagnosis

基　　金：兰州军区医药卫生科研计划课题(CLZ12JA12);新疆自治区青年科技人才专项科研课题(2013QK016);医院博士返院后续课题(2013ZY001)

摘　　要：目的模拟6,000米海拔高度,建立低压低氧性肺动脉高压(HPH)大鼠模型,研究HPH大鼠肺组织中低氧诱导因子-1α(HIF-1α)、内皮素-1(ET-1)和肾上腺髓质素(ADM)的表达及其变化规律。方法将120只SD大鼠随机分为五组,模拟6 000米海拔大气压和氧分压,分别进行低压低氧暴露4天、7天、10天、14天和21天处理,同时设相应时间点对照组(对照组所处海拔为900米),低压低氧暴露时间为24小时/天。于计划的暴露终点采集各组大鼠肺组织标本,HE染色后观察大鼠肺组织的病理学变化,免疫组化法检测肺组织中HIF-1α、ET-1和ADM的表达。结果低压低氧条件分别暴露10天、14天和21天后SD大鼠的平均肺动脉压(mPAP)及肺小动脉血管壁中层壁厚占外径比值(MT%)较同时点相应对照组显著升高(P<0.01);HPH大鼠肺组织中HIF-1α自低压低氧暴露4天后表达即增高,14天后下降,至21天时表达与对照组无显著差异;ET-1在低压低氧10天、14天和21天时其表达较对照组显著升高(P<0.05);ADM在低压低氧4天、7天和10天时表达增加,随后表达降低。结论 HPH大鼠模型肺组织中HIF-1α、ET-1和ADM表达均呈正相关,三种因子可能共同参与了大鼠HPH发生与发展。Objective To study the expression and variation of HIF-1α,ET-1and ADM in lung tissue,by exposing rats to simulated 6000 maltitude to establish hypobaric hypoxia-induced pulmonary hypertension（HPH）animal model.Methods 120 SD rats were placed into a large artificial climate cabin（simulated 6000 maltitude circumstance,24h/day）after they were randomly divided into hypoxic groups for 4days,7days,10 days,14days,21 days and control groups（900maltitude above the sea level）of each corresponding time points;pulmonary tissue samples were analyzed by pathology images analyze software after HE staining;the expression of HIF-1α,ET-1and ADM in lung tissues were detected by immunohistochemistry.Results The mPAP and MT% of SD rats of hypobaric hypoxic for 10 days,14days,21 days groups were significantly higher than the corresponding control groups;the expression of HIF-1αin HPH rats were increased since hypoxic for 4days,and were no significant difference compared with the control groups until hypoxic for 21 days after they were undergone a decrease in 14 days hypoxic group;the expression of ET-1in hypoxic 10 days,14days,21 days groups were increased significantly compared with the normoxia groups;while the expression of ADM was increased in hypoxic 4days,7days,10 days groups,then the expression undergone a reduction afterwards.Conclusion The expression of HIF-1αin HPH rats lung tissues showed a positive correlation between that of ET-1and ADM,and the three factors were involved in the occurrence and development of HPH rats.

关 键 词：低压低氧 肺动脉高压 缺氧诱导因子-1α 内皮素-1 肾上腺髓质素 

分 类 号：R544.1[医药卫生—心血管疾病]