肾上腺髓质素_(1-50)对大鼠慢性低氧性肺动脉高压的调节作用  

Effect of adrenomedullin_(1-50) on chronic hypoxic pulmonary hypertension in rats

作　　者：齐建光[1] 丁亚光[1] 唐朝枢[2] 杜军保[1] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学第一医院心血管研究所

出　　处：《北京大学学报（医学版）》2006年第2期151-154,共4页Journal of Peking University:Health Sciences

基　　金：国家自然科学基会(30300376);国家重点基础研究发展规划项目基金(G2000056905);国家杰出青年科学基金(30425010)资助~~

摘　　要：目的:探讨肾上腺髓质素1-50(ADM1-50)对大鼠慢性低氧性肺动脉高压和肺血管结构重建的作用及其机制。方法:20只雄性Wistar大鼠随机分为对照组(n=7)、低氧组(n=6)和低氧+ADM1-50组(n=7)。对于低氧+ ADM1-50组大鼠,通过皮下埋放微量渗透泵持续给予ADM1-50(300 ng／h)。低氧饲养2周后,以右心导管法测定肺动脉平均压(mPAP),检测右心室与左心室加室间隔的比值[RV／(LV+S)],观测肺血管显微和超微结构的变化,以硝酸还原酶法测定血浆一氧化氮(NO)含量,以敏感硫电极法测量大鼠血浆中硫化氢(H2S)含量。结果:低氧2周后大鼠mPAP较对照组明显增高[(24．9±6．8)mmHg vs(14．3±2．4)mmHg,P<0．01,1 mmHg=0．133 kPa]; RV／(LV+S)也较对照组明显增高[(0．318±0．054)vs(0．182±0．007],P<0．01)。肺动脉显微和超微结构发生明显改变。低氧组大鼠血浆NO和H2S含量明显低于对照组。低氧+ADM1-50组大鼠mPAP明显低于低氧组大鼠 [(14．9±3．0)mmHg vs(24．9±6．8)mmHg,P<0．01];RV／(LV+S)也明显低于低氧组[(0．185±0．011)vs (0．318±0．054),P<0．01]。ADM1-50使低氧大鼠血浆NO和H2S的含量明显升高。结论:ADM1-50可能通过促进低氧大鼠体内NO和H2S的生成,对低氧性肺动脉高压和肺血管结构重建的形成发挥调节作用。Objective： To explore the effect of adrenomedullin1-50 （ADM1-50） on hypoxic pulmonary hypertension and pulmonary vascular structural remodeling and the plasma concentration of nitric oxide （NO） and hydrogen sulfide （H2S） in rats. Methods： Twenty male Wistar rats were randomly divided into control group （n=7）, hypoxic group （n=6） and hypoxic with ADM1-50 group （n =7）. ADM1-50 was subcutaneously administered into rats of hypoxic with ADM1-50 group by mini-osmotic pump （300 ng/h）. After two weeks＇ hypoxic challenge, mean pulmonary arterial pressure （mPAP） was evaluated by using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass [ RV/（ LV ± S） ] was detected. Pulmonary vascular microstructure was measured and the ultrastructural changes in intra-acinar pulmonary arteries were observed. Meanwhile, plasma concentrations of NO and H2S were measured. Results： mPAP was significantly increased in hypoxic rats than that in controls [ （24.9 ±6.8 ） mmHg vs （ 14.3 ± 2.4 ） mmHg, P 〈 0.01,1 mmHg = 0. 133 kPa] ; RV/（ LV ± S） was also significantly increased in hypoxic rats than that in controls [ （0. 318 ±0.054） vs （0. 182 ±0.007 ） ,P 〈0.01 ]. Microstructure and ultrastructure of pulmonary arteries changed obviously in hypoxic rats with the development of hypoxic pulmonary vascular structural remodeling. Meanwhile, plasma NO and H2S concentrations in hypoxic rats were markedly decreased compared with controls. However, mPAP was significantly decreased in hypoxic rats treated with ADMi.5othan that in hypoxic rats [ （14.9 ±3.0） mmHg vs （24.9 ± 6.8） mmHg,P 〈0.01 ] ;RV/（LV ± S） was also significantly decreased than that in hypoxic rats [ （0. 185 ±0.011 ） vs （0.318 ±0.054） ,P 〈0.01 ]. ADM1-50 ameliorated pulmonary vascular structural remodeling of hypoxic rats in association with an increase in plasma NOand HES concentrations. Conclusion： ADM1-50 plays an important ro

关 键 词：肾上腺髓质素 缺氧 高血压 肺性 一氧化氮 硫化氢 

分 类 号：R544.1[医药卫生—心血管疾病]