缺氧诱导因子-1α在野百合碱诱导肺动脉高压大鼠肺组织中的表达及意义

Expression of Hif-1α in the Lungs of Rats with Pulmonary Hypertension Induced by Monocrotaline

目的:观察缺氧诱导因子1α(HIF-1α)在肺动脉高压(肺高压)大鼠肺组织的表达变化,探讨HIF-1α在低氧性肺高压发病中的作用。方法:48只SD大鼠随机分为对照组(CON组)和模型组(MCT组),采用野百合碱一次性皮下注射的方法复制肺高压大鼠模型,右心导管法测定平均肺动脉压(mPAP),计算右心室/(左心室加室间隔),半定量逆转录-聚合酶联反应和Westem blot等方法检测不同时间点(给药后第7、14、21、28天)大鼠肺组织中HIF-1α的表达变化。结果:MCT组大鼠第14天出现右心室肥大,21天mPAP发生显著性改变,且HIF-1α mRNA表达水平于第21天显著升高,westem blot结果显示MCT组大鼠肺组织HIF-1α蛋白含量比CON组大鼠增加。HIF-1α表达增高先于肺高压形成。结论:HIF-1α在肺高压肺组织中表达增加,可能参与了肺高压发病调节,在肺高压形成过程中有重要调节作用。

To observe the expression of hypoxia-inducible factor 1 alpha(H1F-1α) in rat pulmonary in different phases of pulmonary hypertention and to explore the role of HIF-la in the pathogenesis of monocrotaline(MCT group) -induced pulmonary hypertension. Methods: Forty-eight rats were randomly assigned into the control group and monocrotaline-treated group. Monocrataline was delivered as a single subcutaneous injection (60 mg/kg) into male Sprague-Dawley rats weighting about 180 g. The mean pulmonary arterial pressure (mPAP) was measured by right-heart catheterization. Heart weight was measured and a weight ratio of right ventricle ( RV ) to left ventricle plus septum (LV + SP) was calculated. Western blot and Reverse transcription-polymerase chain reaction ( RT-PCR) were used to examine the levels of protein and mRNA of HIF-1α in lungs at different time after MCT group the injection. Results: On the 14th day after MCT group injection, the right ventricular hypertrophy was found, and mPAP increased on the 21 th day after MCT injection. RT-PCR revealed the enhanced expression of HIF-la mRNA in lung tissue on the 21th day after administration of MCT(P < 0. 01) . Western blot analysis demonstrated the increased HIF-la synthetic capacity in lungs of MCT group-treated rats as compared to that of the controls. Conclusion: HIF-1α expression was elevated in the lung of pulmonary hypertensive rats induced by MCT group. HIF-1α might be involved in the pathogenesis of pulmonary hypertension and play an important role in the development of MCT group-induced pulmonary hypertension.