【摘要】 目的研究辛伐他汀对高原性肺动脉高压(PH)大鼠肺血管重构的影响。方法健康雄性SD大鼠40只。体质量180～230g。随机分为4组:对照组(N);高原环境低压低氧模型组(H+P);辛伐他汀低剂量干预组(H+L):2mg/(kg.d);辛伐他汀高剂量干预组(H+H):20mg/(kg.d);除N组外,其他组置于减压舱,模拟海拔5000m高原,23h/d,持续21d;N组在吊压环境中正常饲养3周。分别测定各组肺动脉压、右心室肥大指数;光镜观察肺小动脉管壁厚度百分比、肺非肌性小动脉肌化程度、肺小血管管壁细胞增殖度及新生内膜产生。结果1.除新生内膜指标外,H+P组各项指标均高于余3组(Pa<0.01);2.H+L与H+H组各指标比较无统计学差异(Pa>0.05);3.各组均无新生内膜产生。结论辛伐他汀对低压缺氧所致高原性PH及肺血管重构有防治作用,低压缺氧不能造成新生内膜增生。更多还原

【Abstract】 Objective To investigate the effect of simvastatin on the development of high-altitude environment induced pulmonary hypertension(PH)in rats.Methods Forty healthy male Sprague-Dawley rats(weight 180-250 g)were randomly divided into 4 groups:control group(group N,n=10),in which the rats stayed in orthobaric environment and were fed with vehicle;experimental altitude PH group(group H+P,n=10),in which the animals were kept in hypobaric chamber which simulated the environment of 5 000 metres altitude and treated with vehicle;high dose simvastatin group and low dose simvastatin group(group H+L and group H+H,both n=10),in which rats were kept in hypobaric chamber and treated with low[2 mg/(kg·d)]and high dose[20 mg/(kg·d)] of simvastatin,respectively.On the day 21,the animals were catheterized to record mean pulmonary arterial pressure(mPAP)and then demised as the weight ratio of right ventricle vs left ventricle plus interventricular septum[RV/(LV+IVS)] were measured.Lung tissue were examined microscopically,immunohistochemical stains were used to show α-actin,PCNA and elastin distribution in pulmonary arteries,and morphometric parameters(percentage of vascular wall thickness,muscularization of non-muscularited peripheral pulmonary arterioles)were used to assess the remodeling of small pulmonary arte-ries.Results Rats in group H+P developed significant right ventricular hypertrophy and significant PH.Medial hypertrophy of small pulmonary arteries and peripheral arteriole muscularization and the extent of cell proliferation of pulmonary vessel developed were also more significant in group H+P than control group.Hemodynamic measurements and morphological parameters relevant to PH and pulmonary vascular remodeling were remarkably relieved in,but not significantly different between,rats treated with both low and high dose regimen of simvastatin.There were no neointimal proliferation observed in all the 4 groups.Conclusions Simvastatin is effective in attenuating pulmonary vascular remodeling and suppressing the development of high-altitude environment induced PH and associated pulmonary vascular remodeling.Hypobaric hypoxia cannot induce the neo-intimal proliferation,the landmark of progressive obstructive PH.更多还原