唐古特红景天降低大鼠低氧性肺动脉高压的作用及对ET-1,eNOS mRNA和蛋白表达的影响  

Effect of Hypoxic Pulmonary Hypertension of Rhodiola algida var.tangutica and Related Influence on Gene Expression and Protein Content of ET-1 and eNOS

作　　者：芦殿荣[1] 张树娜 靳国恩[3] 白振忠[3] 永胜[3] 张得钧[3] 王欣佩[3] 杨全余[3] 嘎琴[3] 杨应忠[3] 马兰[3] 王海洁[3] 芦殿香 格日力[3] 

机构地区：[1]中国中医科学院望京医院,北京100102 [2]青海省红十字医院,西宁810000 [3]青海大学医学院高原医学研究中心,西宁810001

出　　处：《中国实验方剂学杂志》2013年第6期274-279,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：中国科学院"西部之光"人才培养计划项目[中国科学院科发人教字2009(236)号];2010年度教育部科学技术研究重点项目(210234)

摘　　要：目的:研究唐古特红景天95%乙醇提取物对大鼠慢性低氧性肺动脉高压(HPH)的作用及其分子机制。方法:雄性Wistar大鼠随机分为对照组、低氧组、低氧+生理盐水组、低氧+低剂量药物组(1.25 g.kg-1.d-1)、低氧+高剂量药物组(2.5 g.kg-1.d-1)5组,每组15只。除对照组外,其余各组动物均置于低压氧舱内(模拟海拔4 500 m的高原环境),每24 h开舱0.5 h进行灌药等处理,连续30 d。检测各组大鼠的肺血流动力学变化、右心室肥厚指数;光镜观察直径50～100μm的肺动脉管壁厚度占外径的百分比(WT%);采用实时荧光定量PCR方法,检测各组动物肺组织内皮素-1(ET-1)和内皮细胞一氧化氮合酶(eNOS)mRNA的表达;采用ELISA法检测各组动物血清ET-1和eNOS蛋白的含量。结果:与低氧对照组和低氧生理盐水组相比,高剂量唐古特红景天干预,具有以下药理作用:①降低大鼠的平均肺动脉压(mPAP),右心室肥厚指数(RV/LV+S),血红蛋白含量(Hb),红细胞压积(Hct)(P<0.01);②减轻大鼠肺动脉的肌化程度(P<0.05);③降低大鼠肺组织ET-1 mRNA表达,上调大鼠肺组织内皮细胞(eNOS)mRNA表达(P<0.05);④降低大鼠血清ET-1蛋白的含量,上调大鼠血清内皮细胞eNOS蛋白的含量(P<0.05)。结论:唐古特红景天对于HPH的形成具有一定的防治作用,其药理作用机制与上调eNOS mRNA和蛋白表达、抑制ET-1 mRNA和蛋白表达有关。Objective： To investigate the pharmacological role of 95% ethanol extract of Rhodiola algida var. tangutica on hypoxic pulmonary hypertension （HPH） and the related molecular mechanism. Method： Seventy-five male Sprague Dawley rats were randomly divided into five groups： control group, hypoxic control group（HC）, hypoxic and physiological saline group（HS）, hypoxic and low dose herb group（1.25 g·kg-1·day-1）, hypoxic and high dose herb group（2.5 g·kg-1·d-1）.The rats were kept in a hypobaric chamber which simulated the environment of a 4 500 m altitude except the control animals.Every 24 h, the hypobaric chamber was opened for 30 min to administrate the herb and the treatment was lasted for 30 days.After that, the hemodynamic changes were recorded and right ventricular hypertrophy index were [RV/（LV＋S）,%] calculated.The lung tissues were stained in HE and morphological parameter of vascular wall thickness（WT, %） was used to assess the remodeling of small pulmonary arteries.The levels of endothelin 1（ET-1） and endothelial nitric oxide synthase（eNOS）mRNA were measured by real-time PCR analysis.The levels of ET-1 and eNOS protein were measured by ELISA method. Result： Compared with the HC and HS group, the high dose of R. algida var.tangutica showed the pharmacologic actions as follows： ① The development of mean pulmonary arterial pressure（mPAP）, RV/LV＋S, hemoglobin（Hb）, haematocrit（Hct） （%） were inhibited（p〈0.01）; ② The muscularization and WT of pulmonary small artery were decreased（P〈0.05）; ③ The level of ET-1 mRNA was decreased and the level of eNOS mRNA was increased in lung（P〈0.05）.④ The level of ET-1 protein content was decreased and the level of eNOS protein content was increased in sera（P〈0.05）. Conclusion： R. algida var.tangutica attenuates hypoxic pulmonary hypertension and remodeling of pulmonary small artery in HPH rats.The mechanisms are likely related to increase in level of eNOS mRNA and protein and decr

关 键 词：唐古特红景天 低氧性肺动脉高压 内皮素-1 内皮细胞氮氧化物合酶 

分 类 号：R285.5[医药卫生—中药学]