烷烃单加氧酶和低氧诱导因子1α在大鼠低氧性肺动脉高压模型肺组织中的表达及其意义  

Altered expressions of alkane monooxygenase and hypoxia inducible factor-1α expression in lungtissue of rat hypoxic pulmonary hypertension

作　　者：邓华君[1] 袁雅冬[1] 

机构地区：[1]河北医科大学第二医院呼吸与危重症医学科,石家庄050000

出　　处：《中华医学杂志》2013年第40期3226-3229,共4页National Medical Journal of China

基　　金：河北省自然科学基金（H2013206403）

摘　　要：目的观察烷烃单加氧酶（AlkB）和低氧诱导因子1α（HIF-1α）在大鼠低氧性肺动脉高压模型肺组织中的表达及其意义。方法20只Wistar大鼠，雌雄不限，按随机数字表法分为对照组、低氧组各10只，应用自制有机玻璃低氧箱，24h持续供应空气和氮气的常压混合气体，控制箱内氧浓度在（10．0±0．5）％。将低氧组大鼠放于缺氧箱内饲养，对照组大鼠呼吸正常空气，与低氧组大鼠放于同一房间以相同饮食饲养。8周后用右心导管法测定大鼠平均肺动脉压（mPAP），称量法计算右心室肥大指数（RVHI），HE染色进行缺氧性肺小动脉重塑观察，Western印迹法和反转录一PCR测定肺组织中AlkB和HIF-1α蛋白及mRNA水平。结果8周后低氧组大鼠肺血管重塑。低氧组大鼠mPAP显著高于对照组[（33．3±1．3）比（11．0±0．7）mmHg（1mmHg=0．133kPa）]，RVHI显著大于对照组（0．4484±0．013比0．2104±0．035）（均P〈0．01）；低氧组AlkB蛋白及mRNA表达均显著低于对照组（0．204±0．010比0．483-t-O．052及0．338±0．085比0．6884±0．020），HIF-1α蛋白及mRNA表达均显著高于对照组（0．893±0．080比0．346±0．008及0．790±0．161比0．422±0．096）（均P〈0．01）。结论低氧环境下，肺组织中的AlkB表达下调，使HIF一1活性增加，参与肺动脉高压的发生发展。Objective To explore the altered expressions of alkane monooxygenase （AlkB） and hypoxia-inducible factor-lot （HIF-1α） in a rat model of hypoxic pulmonary arterial hypertension. Methods Twenty Wistar rats were divided randomly into normal control and hypoxia groups after 1-week adaptive feeding. Hypoxia group was raised in a homemade organic glass tank with a 24-h continuous supply of air and nitrogen atmospheric mixed gas. And the oxygen concentration of （ 10. 0 ± 0. 5 ） % was controlled by oxygen monitoring control system. The control group was maintained in room air. Both groups stayed in the same room with the same diet. After 8 weeks, the level of mean pulmonary pressure （mPAP） was measured by right-heart catheterization, right ventricular hypertrophy index （RVHI） calculated by the ratio of fight ventricle to left ventricle plus septum and hypoxic pulmonary vascular remodeling （HPSR） observed under microscope. And the levels of AlkB and HIF-1α mRNA and protein in lungs were measured by reverse transcriptase-polymerase chain reaction （RT-PCR） and Western blot. Results At 8 weeks post-hypoxia, compared with the control group [ 11.0 ±0. 7 mm Hg （ 1 mm Hg =0. 133 kPa）, O. 210 ±0. 035 ], the levels of mPAP and RVHI in hypoxia group （33.3 ±1.3 mm Hg, 0. 448± 0. 013） increased significantly （ both P 〈0.05）, the expressions of AlkB mRNA and protein in pulmonary tissue decreased significantly （0.338±0.085 vs0.688±0.020, P〈0.01） （0.483 ±0.052 vs 0.204 ±0.010, P0. 01）, and the expressions of HIF-lct mRNA and protein increased significantly （ 0. 790 ± 0. 161 vs 0. 422 ± 0. 096, P 〈 0.01） （0.893±0.080vs0.346±0.008, P〈0.01）. Conclusion The down-regulation of AlkB in lung tissue may increase the activity of HIF-1 to participate in the occurrence and development of pulmonaryhypertension.

关 键 词：高血压 肺性 混合功能氧化酶类 低氧诱导因子1Α 大鼠 

分 类 号：R543.2[医药卫生—心血管疾病]