非洛地平对野百合碱所致大鼠肺动脉高压的作用

The effect and mechanism of felodipine on monocrotaline induced pulmonary hypertension in rats

目的 利用野百合碱 (MCT)制作的大鼠肺动脉高压模型 ,探讨非洛地平对MCT所致肺动脉高压的作用。方法 雄性Wistar大鼠 30只 ,随机分为肺动脉高压模型组 (H组 ) ,非洛地平治疗肺动脉高压组 (F组 ) ,对照组 (C组 ) ,每组 1 0只。予MCT(60mg/kg)复制肺动脉高压大鼠模型后 ,分别给F组及C组大鼠非洛地平 (5mg·kg- 1 ·d- 1 )和生理盐水 (0 .5ml·kg- 1 ·d- 1 )腹腔注射 4周 ,然后测定右室收缩压 (RVSP)和静脉血浆及心、肺组织匀浆内皮素样免疫反应物 (ir ET)、降钙素基因相关肽(CGRP)的含量 ,观察电镜下心肌组织的改变。结果 H、F、C组大鼠RVSP分别为 (44.6± 4 .4)mmHg、(30 .3± 2 .1 )mmHg、(1 8.7± 2 .2 )mmHg ,三组间比较 (P分别 <0 .0 5、<0 .0 1 ) ;H、F组大鼠心、肺组织匀浆中CGRP分别为 (84± 1 9)pg/ml、(2 2± 4)pg/ml、(2 0 .9± 1 .6)pg/ml,(1 4 9± 2 1 )pg/ml、(2 9± 3)pg/ml、(2 7.5± 2 .9)pg/ml,两组间比较 (P <0 .0 5)。非洛地平能显著抑制MCT大鼠模型引起的肺小动脉中膜肥厚 ,减少心肌组织的破坏 ,抑制MCT所致肺动脉高压大鼠模型的血浆及CGRP的减少。结论 长期使用非洛地平能有效防治MCT所致肺动脉高压 ,其作用可能与其Ca2 + 拮抗作用及CGRP降解减少有关。

Objective To explore the effect and the mechanism of felodipine on pulmonary hypertension Methods Adult male Wistar rats were given a single dose of subcutaneous monocrotaline (MCT, 60 mg/kg) to induce the mold of pulmonary hypertension. Felodipine (5 mg/kg) was administered intraperitoneally every day for 4 weeks after MCT injection. The parameters of right ventricular systolic pressure were monitored. The levels of endothelin like immunoreactivity (ir ET) and calcitonin gene related peptide (CGRP) in the plasma and the heart and pulmonary tissues were measured by radioimmunoassay and colorimetric analysis. Right ventricular myocardial tissue was studied under electron microscope. Results Continuous injection of felodipine significantly inhibited the progression of pulmonary artery pressure [(44.6±4.4) mm Hg versus (30.3±2.1) mm Hg,(18.7±2.2) mm Hg]. Histological examination revealed that felodipine effectively prevented pulmonary arterial medial thickening. Felodipine significantly increased the level of CGRP in plasma [(84±19) pg/ml versus 149±21) pg/ml],pulmonary homogenate [ (22±4) pg/ml versus (29±3) pg/ml] and myocardial homogenate [(20.9±1.6) pg/ml versus 27.5±2.9) pg/ml].There was no change in the level of ir ET in the heart and pulmonary tissues. Myocardial damage in the right ventricle was less severe in the felodipine treated group.Conclusions Long term use of felodipine was effective in preventing pulmonary hypertension induced by MCT. The underlying mechanism may be partly related to the increase of CGRP as well as the inhibition of Ca 2+ inflow. The results indicate that felodipine may be considered for clinical trials in the treatment of primary pulmonary hypertension.