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Apelin 对大鼠低氧性肺动脉高压的作用及与NO 途径的关系

毛孙忠, 洪林, 胡良冈, 范小芳, 张丽, 郭益民, 龚永生

温州医学院 肺心病研究室；生理学教研室； 机能实验中心、机能实验学教研室，温州 325035

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% O2，8 h/d，6 d/ 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10 nmol/kg，28 d)。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(nitric oxide synthase, 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0.5 nmol/L、5 nmol/L 和10 nmol/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。

关键词： a p e l i n ; 一氧化氮; 低氧; 高血压; 肺性

分类号：R363.2；R541.5

[Effect of apelin on hypoxic pulmonary hypertension in rats: role of the NO pathway.] [Ariticle in Chinese]

MAO Sun-Zhong, HONG Lin, HU Liang-Gang, FAN Xiao-Fang, ZHANG Li1, GUO Yi-Min, GONG Yong-Sheng

Institute of Cor Pulmonale； Department of Physiology； The Center of Functional Experiment, Wenzhou Medical College, Wenzhou 325035, China

Abstract

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. Larginine (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.

Key words: apelin; nitric oxide; hypoxia; hypertension, pulmonary;

收稿日期：2009-06-15　　录用日期：2009-07-22

通讯作者：龚永生　　E-mail: fxbwzmc@126.com

引用本文：

毛孙忠, 洪林, 胡良冈, 范小芳, 张丽, 郭益民, 龚永生. Apelin 对大鼠低氧性肺动脉高压的作用及与NO 途径的关系[J]. 生理学报 2009; 61 (5): 480-484.

MAO Sun-Zhong, HONG Lin, HU Liang-Gang, FAN Xiao-Fang, ZHANG Li1, GUO Yi-Min, GONG Yong-Sheng. [Effect of apelin on hypoxic pulmonary hypertension in rats: role of the NO pathway.] [Ariticle in Chinese] . Acta Physiol Sin 2009; 61 (5): 480-484 (in Chinese with English abstract).