G蛋白竞争性抑制肽GCIP-27对野百合碱所致肺动脉高压影响的研究

GCIP-27 inhibits the development of pulmonary hypertension in monocrotaline-treated rats

目的探讨G蛋白竞争性抑制性肽GCIP-27对野百合碱（MCT）所诱导的大鼠肺动脉高压的影响及其作用机制。方法将36只SD大鼠随机分为正常组（n=8）、MCT组（n=12）、GCIP-27低剂量组（30μg/kg,n=8）和GCIP-27高剂量组（90μg/kg,n=8）。后3组大鼠一次性给予颈背部皮下注射MCT50mg/kg制造肺动脉高压模型,GCIP-27低剂量组和GCIP-27高剂量组于造模后1-21d经腹腔注射分别给予GCIP-27 30μg/kg和90μg/kg,每天两次。造模第22天,右心导管术测肺动脉收缩压、肺动脉舒张压、平均肺动脉压；称取肺和右心室重量,并计算肺和右心室的相对重量（肺重/体重,右心室重/体重）；HE染色观察肺动脉形态学改变；免疫组化观察肺动脉平滑肌细胞核增殖抗原（PCNA）的表达情况。结果高剂量GCIP-27能抑制MCT诱导的肺动脉收缩压及平均肺动脉压的升高（P〈0.05）,并抑制MCT所诱导的肺相对重量及右心室相对重量的增加（P〈0.05）,改善肺动脉重构,抑制肺动脉平滑肌PCNA抗原的过表达。结论GCIP-27（90μg/kg）能降低MCT诱导的肺动脉高压,其机制与肺动脉平滑肌增殖受抑有关。

Objective To explore the effect and the mechanism of G protein competitive inhibitory polypeptide （GCIP-27） on pulmonary artery hypertension induced by monocrotaline （MCT） in rats. Methods Thirty-six male Sprague-Dawley rats were randomly divided into four groups： normal control group （n=8）, MCT treatment group （n=12）, low dose of GCIP-27 treatment group（30μg· kg^-1） （n =8） and high dose of GCIP 27 treatment group（90μg· kg^-1）（n=8）. Rats were given a single dose of MCT（50μg· kg^-1） subcuta neouly to induce pulmonary artery hypertension. GCIP-27 was administered （twice daily, ip） from day I to day 21. Hemodynamic parameters, such as pulmonary artery systolic pressure （PASP）, pulmonary artery diastolic pressure （PADP） and mean pulmonary artery pressure （MPAP）, were measured by a right cardiac catheter at the 22nd day. The right ventricle and the lung were respectively weighed. The relative weight ratio of right ventricle or that of lung to body weight was calculated respectively. The morphology of the pulmonary artery was studied with H＆E light microscopy. To assess the presence of proliferating ceil nuclear antigen （PCNA） in pulmonary artery smooth muscle, immunohistoehemical analysis was performed on paraffin-embedded left lung tissue with the anti-PCNA primary antibody. Results Compared with that of MCT group, GCIP-27 （90μg· kg^-1） significantly inhibited the elevated PASP and MPAP （P〈0.05）, and improved the relative weight ratio of right ventricle and lung （P〈0.05 or P〈0.05）. Histological examination revealed that GCIP-27 effec tively prevented thickening of the intima of the pulmonary artery（P〈0.05）. Immunohistochemical analysis showed GCIP-27 effectively reduced the PCNA over-expression in pulmonary artery smooth muscle. Conclusions GCIP-27 （90μg· kg^-1） can inhibit the development of pulmonary hypertension in MCT treated rats. The mechanism may be related to the reduced proliferation of pulmonary artery smooth muscle.