野百合碱对大鼠肺动脉α-SMA抗原过表达和Ⅷ因子抗原低表达的影响

Effect of Monocrotaline on Over-expression of α-Smooth Muscle Actin and Low-expression of Ⅷ Factor Antigen on Pulmonary Arteries in Rats

目的研究野百合碱(monocrotaline,MCT)对肺动脉压的影响及其发病机制。方法雄性SD大鼠18只,随机分为两组,正常组(n=7),模型组(n=11)。模型组通过一次性颈背部皮下注射MCT50mg.kg-1,22d后,通过右心导管法,用Powerlab记录大鼠肺动脉收缩压(PASP)、肺动脉舒张压(PADP)、平均肺动脉压(MPAP)、右室收缩压(RVSP)的变化;称定右室游离壁(RV)质量和左室加室间隔(LV+SEP)质量,计算右心肥大指数(RVHI=RV/LV+SEP);称定肺质量,并计算其与体质量的相对质量指数(LI),用免疫组化方法,观察石蜡包埋左肺组织的肺小动脉α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)抗原的表达及其肺血管内膜Ⅷ因子抗原的表达。结果50mg.kg-1MCT可显著升高PASP、PADP、MPAP、RVSP、RVHI和LI(P<0.01);MCT使肺小动脉α-SMA抗原过表达,肺小动脉重构;使肺血管内膜Ⅷ因子抗原低表达,肺毛细血管数目减少。结论50mg.kg-1MCT可以成功塑造肺动脉高压模型,其造模机制不仅与肺动脉的重构相关,而且还与肺毛细血管的数量明显减少相关。

Objective To study the effect and mechanisms of monocrotaline（MCT）on the pulmonary arterial pressure.Methods Eighteen Sprague-Dawley male rats were randomly divided into normal control group（n=7）and model group（n=11）.Animals in the model group were given with a single dose of MCT（50 mg·kg^-1）subcutaneously.Hemodynamic parameters such as pulmonary arterial systolic pressure（PASP）,pulmonary artery diastolic pressure（PADP）,mean pulmonary arterial pressure（MPAP）and right ventricular systolic pressure（RVSP）were measured by right catheterization with Powerlab on the 22nd day.The heart was separated into the right ventricle（RV）and left one with septum（LV＋SEP）and weighed separately.RVHI was calculated as the weight ratio of RV/（LV＋SEP）.The weight ratio of lung to body weight was calculated.Immunohistochemical analysis was performed on paraffin-embedded left lung tissue to detect the expression of α-smooth muscle actin（α-SMA）and Ⅷ factor on pulmonary endangium.Results The PASP,PADP,MPAP and RVSP were elevated significantly（P〈0.01）in the 50 mg·kg^-1MCT-treated rats as compared with the normal control animals.The similar changes were observed for the values of LI and RVHI（P〈0.01）.Immunohistochemical analysis showed MCT effectively increased the expression of α-SMA antigen in pulmonary arteries（PAs）and lead to PAs remodeling.In addition,MCT also could effectively decrease the expression of Ⅷ factor antigen in the endomembrane of PAs and lessen the number of pulmonary capillary.Conclusion MCT（50 mg·kg^-1）can satisfactorily make the model of pulmonary artery hypertension and the mechanism of which may be related to the PA remodeling and the loss of pulmonary capillary.