Apelin对大鼠低氧性肺动脉高压的作用及与NO途径的关系  

Effect of apelin on hypoxic pulmonary hypertension in rats:role of the NO pathway

作　　者：毛孙忠[1] 洪林[1,2] 胡良冈[1,3] 范小芳[1,3] 张丽[1] 郭益民[1,2] 龚永生[1,2,3] 

机构地区：[1]温州医学院肺心病研究室机能实验学教研室,温州325035 [2]温州医学院生理学教研室机能实验学教研室,温州325035 [3]温州医学院机能实验学教研室,温州325035

出　　处：《生理学报》2009年第5期480-484,共5页Acta Physiologica Sinica

基　　金：supported by the National Basic Research Development Program of China(No.2006CB504127);the Natural Science Foundation of Zhejiang Province,China(No.206464)

摘　　要：本文旨在探讨外源性apelin对大鼠低氧性肺动脉高压和肺血管重构的作用及其机制。将24只雄性Sprague-Dawley大鼠随机均分为正常对照组(NC)、常压低氧4周组(HH)和常压低氧4周+apelin组(HA)。常压低氧4周(9%～11%O2,8h/d,6d/周)制备慢性低氧性肺动脉高压模型。HA组大鼠于低氧处理前,通过皮下埋植微量渗透泵持续给予[pGlu]apelin-13(每天10nmol/kg,28d)。离体孵育大鼠肺动脉,用同位素法测定其对[3H]-L-精氨酸(L-Arg)的摄取率,用化学比色法检测肺组织一氧化氮合酶(nitricoxidesynthase,NOS)活性,用硝酸还原酶法测定血浆和肺组织中NO代谢产物亚硝酸盐/硝酸盐(NO2-/NO3-)的含量。结果显示,HH组平均肺动脉压、右心室与左心室加室间隔重量比、肺细小肌型动脉相对中膜厚度和相对面积均显著高于NC组(均P<0.01),而HA组以上指标均低于HH组(P<0.05或P<0.01);与HH组相比,HA组的肺动脉薄片对0.5nmol/L、5nmol/L和10nmol/L[3H]-L-Arg摄取率分别高121.4%(P<0.01)、85.0%(P<0.05)和61.5%(P<0.05),肺组织cNOS活性高74.3%而iNOS活性低25.0%(均P<0.01)),肺组织和血浆NO2-/NO3-含量分别高97.6%和48.0%(均P<0.05)。以上结果表明,apelin对低氧性肺动脉高压和肺血管重构有干预作用,其机制可能与促进L-Arg/NOS/NO途径有一定的关系。To investigate the effectiveness and mechanism of apelin against pulmonary hypertension and pulmonary vascular remodeling induced by hypoxia in rats, 24 male Sprague-Dawley rats were randomly divided into normal control （NC） group, 4-week hypoxia （HH） group and 4-week hypoxia with apelin （HA） group （each n=8）. The rats of hypoxic group were placed in an isobaric hypoxic chamber, in which O2 and CO2 content was maintained at 9%-11% and 〈3%, respectively, for 4 weeks （8 h/d, 6 d/week）. [pGlu]apelin- 13 （10 nmol/kg per day, 28 d） was administered subcutaneously by osmotic mini-pump before hypoxia treatment in HA group. L- arginine （L-Arg） uptake of pulmonary artery was assay by [3H]-L-Arg, while nitric oxide synthase （NOS） activity of pulmonary tissue, and nitrate/nitrite （NO2-/NO3-） concentrations in pulmonary tissue and plasma were detected by colorimetric technique and nitrate reductase method, respectively. The results showed that mean pulmonary arterial pressure, the ratio value of right ventricle weight to left ventricle plus septum weight, the relative medial thickness, and the relative medial area of pulmonary arterioles were higher in HH group than those in NC group （all P〈0.01）, while these indices were lower in HA group than those in HH group （P〈0.05 or P〈0.01）. Compared with those in HH group, the uptake of 0.5, 5 and 10 nmol/L [3H]-L-Arg in pulmonary artery in HA group increased by 121.4% （P〈0.01）, 85.0% （P〈0.05） and 61.5% （P〈0.05）, respectively; cNOS activity of pulmonary tissue increased by 74.3%, while iNOS activity decreased by 25.0% （all P〈0.01）; and NO2/NO3-concentrations in pulmonary tissue and plasma increased by 97.6% and 48.0% （all P〈0.05）, respectively. Taken together, our results suggest that apelin has a prophylactic effect against hypoxic pulmonary hypertension in rats, and that the mechanism of this effect is possibly associated with activation of the L-Arg/NOS/NO pathway.

关 键 词：APELIN 一氧化氮 低氧 高血压 肺性 

分 类 号：R363.2[医药卫生—病理学] R541.5[医药卫生—基础医学]