G蛋白抑制肽抑制野百合碱所诱导的右室重构

GCIP-27 inhibits the right ventricle remodeling in monocrotaline-treated rats

目的探讨G蛋白抑制肽(GCIP-27)对野百合碱(monocrotaline,MCT)所诱导右室重构的作用及相关机制。方法SD大鼠随机分为正常组、MCT模型组、GCIP-27低剂量组(30μg·kg-1)和GCIP-27高剂量组(90μg·kg-1)。MCT造模后1d～21d给GCIP-27(ip,bid)。造模d22右心导管术测肺动脉压;称右心室自由壁重(RV)及左心室加室间隔重(LV+S),计算右心肥大指数[RVHI=RV/(LV+S)];HE染色光镜观察右室形态学改变;电镜观察右室超微结构变化;免疫组化观察右室心肌细胞核增殖抗原(PCNA)的表达。结果GCIP-27能明显抑制MCT所引起RVHI的升高、右室心肌细胞肥大及线粒体肿胀、变性和右室心肌细胞PCNA的过表达。高剂量GCIP-27降低MCT所诱导的肺动脉收缩压,平均肺动脉压的升高(P<0.05或P<0.01),但低剂量GCIP-27(30μg·kg-1)仅降低肺动脉收缩压的升高(P<0.05)。结论GCIP-27能明显抑制MCT诱导的右室重构。

Aim The effect and mechanism of GCIP-27 on the right ventricle remodeling by monocrotaline （MCT） were explored. Methods Sprague-Dawley rats were randomly divided into the normal group, MCT group and the low and high dose GCIP-27 treatment group. Pulmonary arterial systolic pressure （PASP）, pulmonary artery diastolic pressure （PADP） and mean pulmonary arterial pressure （MPAP） were measured by fight cardiac catheter on the 22 th day. RV and left ventricle plus septum were weighed separately. Right ventricular hypertrophy index （RVHI） was measured by the weight ratio of RV to left ventricle plus septum. The histological examination of right ventricle were executed by light microscope and transmission electron microscope. Immunohistochemical analysis was performed on the paraffin-embedded right ventricle tissue using the anti-PCNA primary antibodies. Results GCIP-27 （90ug·kg^-1） significantly inhibited the progression of PASP and MPAP and GCIP-27 （30ug·kg^-1 ） only reduced the progression of PASP. GCIP-27 significantly inhibited the increase of RVHI and cardiomyocytes hypertrophy versus MCT group. The swollen and misshapen mitochondria could be improved by GCIP-27. And the PCNA expression caused by MCT could be inhibited by GCIP-27 in right ventricle cardiomyocytes. Conclusion GCIP-27 can attenuate the fight ventricular remodeling siginificantly in monocrotaline-treated rats.