辛伐他汀对野百合碱诱导肺动脉高压大鼠血红素加氧酶1表达的影响

目的观察辛伐他汀对野百合碱致肺动脉高压大鼠的肺循环血流动力学和肺小动脉重构的作用,以及对肺组织血红素加氧酶1（HO-1）表达的影响。方法 52只SD大鼠随机分为五组：正常对照组、辛伐他汀对照组、肺动脉高压模型组、辛伐他汀治疗组和血红素加氧酶抑制剂（ZnPP）组。右心导管测定肺动脉平均压（mPAP）、右心室收缩压（RVSP）。以右心室/（左心室＋室间隔）的质量比（RVHI）作为评价右心室肥厚的指标。病理图像分析系统测定并计算动脉管壁面积百分比和动脉管壁直径百分比以评价肺血管重构严重程度。免疫组化方法观察HO-1在大鼠肺组织中表达部位,通过免疫印迹法半定量测定肺组织HO-1蛋白表达水平。结果与模型组比较,辛伐他汀治疗组mPAP、RVHI显著降低（35.63±5.10）mm Hg比（65.78±15.51）mm Hg,0.33±0.05比0.53±0.06,P〈0.05]。辛伐他汀治疗减轻了肺血管重构,动脉管壁面积百分比和动脉管壁直径百分比分别为（50.78±9.03）%和（43.75±4.23）%,较模型组明显降低（65.92±7.19）%,（52.00±5.35）%]。免疫组化显示在肺动脉高压模型组,HO-1主要在肺泡巨噬细胞中呈阳性表达。在辛伐他汀治疗组,HO-1表达明显增高,尤其在血管平滑肌细胞和肺泡巨噬细胞呈强阳性表达。HO-1的抑制剂ZnPP部分抑制辛伐他汀对PH大鼠的作用,其mPAP为（52.88±17.45）mm Hg,动脉管壁面积%为（50.78±9.03）%,动脉管壁直径百分比为（52.00±5.35）百分比。结论辛伐他汀减轻野百合碱诱导大鼠的肺动脉高压,抑制肺血管重构改变,其作用机制与增加HO-1表达有关。

Simvastation Induces Heme Oxygenase-1 Expression in Monocrotaline-Induced Pulmonary Hypertension Rats

Objective To investigate the effects of simvastatin on monocrotaline-induced pulmonary hypertension in rats,and explore the potential mechanism of simvastatin by blocking heme oxygenase-1（HO-1） expression.Methods 52 male Sprague-Dawley rats were randomly divided into five groups,ie.a control group,a simvastatin control group,a pulmonary hypertension model group,a simvastatin treatment group,a ZnPP（chemical inhibitor of HO） group.Mean pulmonary arterial pressure（mPAP） and right ventricular systolic pressure（RVSP） were detected by right heart catheter at 5th week.Right ventricular hypertrophy index（RVHI） was calculated as the right ventricle to the left ventricle plus septum weight.Histopathology changes of small intrapulmonary arteries were evaluated via image analysis system.Immunohistochemical analysis was used to investigate the expression and location of HO-1.HO-1 protein level in lung tissue were determined by western blot.Results Compared with the model group,simvastatin treatment decreased mPAP and RVHI significantly （35.63±5.10）mm Hg vs.（65.78±15.51）mm Hg,0.33±0.05 vs.0.53±0.06,both P0.05].Moreover,simvastatin treatment partially reversed the increase of arterial wall area and arterial wall diameter （50.78±9.03）% vs.（65.92±7.19）%,（43.75±4.23）% vs.（52.00±5.35）%,both P0.01）.In the model group,HO-1 staining was primarily detected in alveolar macrophages.Simvastatin treatment increased HO-1 protein expression significantly,especially in the thickened smooth muscle layer and alveolar macrophages.Inhibiting HO-1 expression using ZnPP resulted in a loss of the effects of simvastatin.mPAP in the ZnPP group was（52.88±17.45）mm Hg,while arterial wall area and arterial wall diameter were（50.78±9.03）% and（52.00±5.35）%,respectively. Conclusions Simvastatin attenuates established pulmonary arterial hypertension and pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension rats.The effect of simvastatin is associated with HO-1.