肾上腺髓质素对大鼠异丙肾上腺素心肌坏死的保护作用  

Protective effect of adrenomedulin (13～52) on isoproterenol induced myocardial injury in rats

作　　者：杨军[1,2] 赵东[1,2] 常英姿[1,2] 田青[1,2] 赵云涛[1,2] 石湘云[1,2] 张肇康[1,2] 唐朝枢[1,2] 

机构地区：[1]北京医科大学心血管研究所海军总医院心内科 [2]美国PHOENIX药物有限公司

出　　处：《中国药理学通报》1996年第6期530-533,共4页Chinese Pharmacological Bulletin

摘　　要：在大鼠皮下注射异丙肾上腺素（６９μｍｏｌ·ｋｇ－１·ｄ－１）造成的心肌坏死模型上，用肾上腺髓质素（１３～５２）（１０ｎｍｏｌ·ｋｇ－１·ｄ－１）治疗，明显减轻由异丙肾上腺素引起的心肌损伤，抑制血浆内皮素水平的升高和细胞内酶的漏出，减轻心肌水肿程度，阻止脂质过氧化物的形成、心肌钙聚积以及血管、心肌组织ｃＧＭＰ含量下降，明显改善心３功能，表现了强大的心肌保护作用。一氧化氮合酶竞争性抑制剂左旋硝基精氨酸（Ｌ－ＮＮＡ）完全阻断肾上腺髓质素的保护作用。结果表明，肾上腺髓质素对心肌缺血损伤有细胞保护作用。Adrenomedulin (AdM) is a newly isolated peptide with hypotensive activity in normotensive rats. The cardio protective action of human AdM (13～52), a C terminal fragment of AdM (1～52),was observed on the myocardial injury model produced by subcutaneous injection of isoproterenol (69 μmol·kg -1 ) into rats. Treatment with human AdM (13～52) (10 nmol·kg -1 ·d -1 , iv.) significantly ameliorated isoproterenol induced myocardial necrosis inhibited elevation of plasma endothelin immunoreactivity level, leakage of intracellular enzyme (lactate dehydrogenase) and release of myocardial lipid perox 1General Navy Hospital, Beijing 100037 2Phoenix Pharmaceuticals, Belmont, CA 94002 4041, USA idation products (MDA), decreased myocardial MDA and calcium content, and markedly prevented the decrease of cGMP levels in myocardium and vessel tissue, and obviously improved cardiac function. However, co administration of AdM (13～52) and LNNA, a specific nitric oxide synthase inhibitor, completely blocked the cardioprotective action of AdM (13～52), suggesting that the cardioprotective action of adrenomedullin may be mediated by NO.

关 键 词：肾上腺髓质素 异丙肾上腺素 心肌损伤 心肌保护 

分 类 号：R972[医药卫生—药品] R965.1[医药卫生—药学]