Gax在肺动脉高压大鼠肺动脉中的表达变化

目的:使用低氧及野百合碱(monocrotaline,MCT)诱导的两种肺动脉高压(pulmonary arterialhypertension,PAH)大鼠模型,观察生长终止特异性同源盒(growth arrest-specific homeobox,Gax)在肺动脉的表达变化。方法:Sprague Dawley大鼠随机分为四组:低氧模型组(n=16)、低氧对照组(n=16)、MCT模型组(n=16)及MCT对照组(n=16)。采用插管法测定大鼠的右心室压力及肺动脉压力。右心室质量除以左心室和室间隔质量,计算右心肥厚指数。采用定量RT-PCR法测定肺动脉主干及肺组织Gax mRNA表达;采用Western免疫印迹法测定肺动脉主干Gax蛋白表达;免疫组织化学染色观测Gax在肺内的分布及表达变化。结果:低氧模型组及MCT模型组大鼠的右心压力、肺动脉压力及右心肥厚指数均显著高于相应对照组(P<0.01),两种模型大鼠的肺动脉血管均出现明显重构。与对照组比较,Gax mRNA在两种模型组大鼠的肺组织表达降低(P<0.05),而在肺动脉主干表达升高(P<0.05)。Gax蛋白在肺内主要表达在微小动脉。与对照组比较,两种模型组大鼠的肺动脉主干和肺微小动脉Gax蛋白表达均升高(P<0.05),而肺组织Gax蛋白表达下降(P<0.05)。结论:Gax主要表达在肺微小动脉,在PAH发生时表达上调。

Change of Gax expression in pulmonary arteries of pulmonary arterial hypertensive rats

Objective: To study the change of growth arresting-specific homeobox(Gax) expression in pulmonary arteries in rat models of pulmonary arterial hypertension(PAH) induced by hypoxia or monocrotaline(MCT).Methods: Sprague Dawley rats were randomly divided into 4 groups: a hypoxia PAH group(n=16),a hypoxia control group(n=16),a MCT PAH group(n=16) and a MCT control group(n=16).Pressure in the right ventricle and pulmonary artery was measured by the catheterization method.Right ventricular hypertrophy index was calculated by right ventricular weight divided by left ventricular weight(left ventricle plus septum weight).Level of Gax mRNA in lung and pulmonary artery trunk was determined by quantitative RT-PCR.Expression of Gax protein was determined by Western blot.Distribution and change of Gax in lung was detected by immunohistochemistry.Results: Right ventricle pressure,pulmonary artery pressure and right ventricular remodeling index were significantly higher in the hypoxia PAH group and the MCT PAH group than those in the control(P<0.01).In the hypoxia PAH group and the MCT PAH group,pulmonary vascular remodeling occurred,and the expression of Gax mRNA was deceased in the lungs,but increased in the pulmonary artery trunk(P<0.05).Gax was expressed mainly at pulmonary arterioles and up-regulated in pulmonary arterioles and pulmonary artery trunk,but down-regulated in lungs in the hypoxia PAH group and the MCT PAH group(P<0.05).Conclusion:Gax is mainly expressed in pulmonary arterioles and up-regulated in pulmonary arteries of PAH rats.