腺苷受体激动剂降低低氧大鼠肺动脉高压及对诱导型一氧化氮合酶-一氧化氮和肾素-血管紧张素的影响  

Adenosine receptors agonists mitigated PAH of rats induced by chronic hypoxia through reduction of renin activity/angiotensin II levels and increase of inducible nitric oxide synthase-nitric oxide levels

作　　者：谭建新[1] 黄秀兰[1] 王波[1] 方兴[1] 黄迪南[2] 

机构地区：[1]524023湛江,广东医学院附属医院儿科 [2]524023湛江,广东医学院附属医院生化研究所

出　　处：《中华儿科杂志》2012年第10期782-787,共6页Chinese Journal of Pediatrics

基　　金：广东省自然科学基金（8152402301000010）

摘　　要：目的探讨外源性腺苷治疗低氧肺动脉高压的作用和机制。方法将56只sD大鼠按随机数字表随机分为7组，每组8只，分别为常氧组、低氧组、腺苷处理组[在低氧条件下予以腺苷处理，腺苷剂量150μg/（kg·min）]、腺苷A1受体激动剂CPA处理组[低氧条件下予以CPA处理，CPA剂量20μg/（kg·min）]、CPA＋选择性腺苷A1受体拮抗剂DPCPX处理组[低氧条件下同时予CPA和DPCPX处理，CPA剂量同前，DPCPX剂量25μg/（kg·min）]、腺苷A2b受体激动剂NECA处理组[低氧条件下予以NECA处理，NECA剂量30μg/（kg·min）]、NECA＋选择性腺苷A2b受体拮抗剂MRS处理组[低氧条件下予以NECA和MRS1754联合处理，NECA同前，MRS1754剂量50μg/（kg·min）]。给药14d后测量平均肺动脉压力（mPAP），然后取血用放射免疫法测血浆肾素活性（RA）、血管紧张素Ⅱ（AngII）、内皮素1水平，比色法测定一氧化氮（NO）浓度，取肺动脉作免疫组化染色测定肺动脉增殖细胞核抗原（PCNA）和诱导型一氧化氮合酶（iNOS）的蛋白表达。结果（1）腺苷处理组和CPA、NECA处理组mPAP[分别为（21．17±3．56）mmHg（1mmHg=0．133kPa）、（22．88±2．95）mmHg、（19．81±2．39）mmHg]均低于低氧组大鼠mPAP（31．38±3．42）mmHg，差异有统计学意义（P均〈0．05）；（2）低氧组血浆RA和AngⅡ水平分别为（2．51±0．25）ng／（ml-h）和（83．01±9．38）pg／ml，高于常氧组（P均〈0．05）。腺苷、CPA和NECA处理后血浆RA和AngⅡ水平均低于低氧组（P均〈0．05）；（3）腺苷处理后肺动脉血管壁厚度低于低氧组（P〈0．05）；CPA处理对低氧所致肺动脉血管壁厚度无影响，NECA处理则降低低氧所致肺动脉血管壁厚度，与低氧组比较差异有统计学意义（P〈0．05）；（4）低氧组肺动脉血管iNOS阳性细胞数明显高于常氧组（23．75±7．91m8．00±2．20，P〈0．05）；腺苷、CPA和NECA处理�Objective Recent studies showed that adenosine played important roles in vasodilation. This study aimed to investigate the effects of adenosine, its A1 and A2b receptor agonists on pulmonary artery hypertension （PAH） induced by chronic hypoxia in rats by continuously subcutaneous administration with an osmotic pump for 14 days, and to see if rennin angiotensin system and inducible nitric oxygen synthase （iNOS）/nitric oxide （NO） mediate the effects. Method Fifty-six male SD rats were randomly assigned to seven groups. Each group included eight rats. They were normoxic group, hypoxic group, adenosine-treated group [ adenosine was administered at a dose of 150 μg/（kg·min） under the hypoxic conditions, adenosine A1 receptor agonist CPA-treated group [ CPA was administered at a dose of 20 μg/（kg·min）under the hypoxic condition], CPA pills selective adenosine A1 antagonist DPCPX-treated group [ CPA and DPCPX were administered simultaneously under the hypoxic condition, the dose of CPA was the same as the above, and the dose of DPCPX was 25 μg/（kg·min） ], adenosine A2b receptor agonist NECA- treated group [ NECA was administered at a dose of 30 μg/（kg·min） under the hypoxic condition], NECA plus selective adenosine A2b receptor antagonist MRS-treated group [ NECA and MRS1754 were administered simultaneously under the hypoxic condition, the dose of NECA was the same as the above, and the dose of MRS1754 was 50μg/（kg·min）]. Osmotic pumps containing adenosine or selective adenosine A1 receptor agonist （CPA）, or nonselective but potent adenosine A2b receptor agonist （NECA） were placed subcutaneously 7 days after hypoxia and continuously administered the agents for 14 days. Mean pulmonary artery pressure （mPAP） was detected after administration of the agents. Then blood samples were taken from heart for measurement of renin activity, angiotensin Ⅱ （Ang Ⅱ ） and endothelin-1 （ET-1） concentration by radioimmunoassay, NO by measuring nitrate. Small pulmonary arter

关 键 词：低氧 腺苷 高血压 肺性 

分 类 号：R725.4[医药卫生—儿科]