缺氧诱导因子在高肺血流性肺动脉高压大鼠肺组织中的动态变化及意义  

Changes of hypoxia inducible factors in rats with high pulmonary blood flow-induced pulmonary artery hypertension

作　　者：刘阳[1] 于晴[1] 张敬[1] 孙茫[1] 李上莹莹 涂生芬[1] 

机构地区：[1]重庆医科大学附属儿童医院麻醉科,儿童发育疾病研究教育部重点实验室,儿童发育重大疾病国家国际科技合作基地,儿科学重庆市重点实验室,重庆400014

出　　处：《第三军医大学学报》2018年第2期116-121,共6页Journal of Third Military Medical University

基　　金：国家临床重点专科建设项目(国卫办医函[2013]544号);重庆市卫计委高端人才后备项目(2015HBRC007);重庆市自然科学基金(CSTC2012jjA10036)

摘　　要：目的观察缺氧诱导因子(hypoxia inducible factors,HIFs)在高肺血流性肺动脉高压大鼠肺组织的动态表达,探讨HIF-1α、HIF-2α在高肺血流性肺动脉高压形成过程中的作用。方法 64只6周龄雄性健康SD大鼠采用随机数字法均分为假手术组与肺动脉高压组,肺动脉高压组大鼠通过腹主动脉-下腔静脉分流法建立高肺血流性肺动脉高压模型,在两组大鼠术后第4、8、12、16周测量平均肺动脉压力(mean pulmonary artery pressure,mPAP)、右心室肥厚指数(right ventricular hypertrophy index,RVHI)及肺血管形态学观察,Western blot检测肺组织HIF-1α、HIF-2α蛋白表达,RT-PCR检测HIF-1αmRNA、HIF-2αmRNA的表达。结果肺动脉高压组大鼠术后mPAP及RVHI随时间延长持续增高,肺动脉形态学变化与mPAP变化一致;肺动脉高压组大鼠肺组织HIF-1α、HIF-2α蛋白表达在术后随着时间的延长,均呈现先升高后下降的趋势,于术后8、12周明显高于同时间点对照组(P<0.05);HIF-1αmRNA、HIF-2αmRNA的表达亦呈现先升高后下降的趋势,于术后8、12周明显高于同时间点对照组(P<0.05)。结论 HIF-1α和HIF-2α可能在大鼠高肺血流性肺动脉高压形成过程中的肺血管病变可逆阶段发挥了一过性的血管保护作用,但仍无法遏制肺动脉高压的形成。ObjectiveTo evaluate the role of hypoxia inducible factors （HIF1α and HIF2α） in the pathogenesis of high blood flowinduced pulmonary artery hypertension （PAH） in rats. MethodsSixtyfour healthy male SD rats （6 weeks） were randomly divided into shamoperated group and pulmonary hypertension group. A lefttoright shunt PAH model was established by creating an arterialvenous shunt between the abdominal aorta and the inferior vena cava in pulmonary hypertension group. The mean pulmonary arterial pressure （mPAP） and right ventricle hypertrophy index （RVHI） were measured and the vascular morphology was observed in 4, 8, 12, and 16 weeks after the operation. The mRNA and protein expressions of HIF1α and HIF2α in the lung tissues were determined using RTPCR and Western blotting. ResultsCompared with the shamoperated rats, the rats with PAH showed a gradual increase of mPAP and RVHI over time, and significant increases of mPAP （P〈0.05） and RVHI （P〈0.05） occurred at 12 weeks and 16 weeks after the operation, respectively. The rats with PAH also exhibited severer pathological damages in the lungs than the shamoperated rats. Compared with the rats in the sham operation group, the rats with PHA showed significantly increased levels of HIF1α and HIF2α proteins at 8 and 12 weeks after the operation, respectively （P〈0.05）, with also significant increases in the mRNA levels of HIF1α and HIF2α （P〈0.05）. In rats with PAH, the expressions of HIF1α and HIF2α at both protein and mRNA levels showed an initial increase and a subsequent decrease over time after the operation. ConclusionIn rats with high pulmonary blood flowinduced PAH, HIF1α and HIF2α may offer transient vascular protection in the reversible phase during the formation of pulmonary vascular lesions, but they are unable to prevent the occurrence of pulmonary hypertension.

关 键 词：缺氧诱导因子-1Α 缺氧诱导因子-2Α 高肺血流性肺动脉高压 

分 类 号：R322.35[医药卫生—人体解剖和组织胚胎学] R341[医药卫生—基础医学]