中文摘要：

目的在异丙基肾上腺素（isoproterenol，ISO）诱导的大鼠急性心肌损伤的模型上探讨Intermedin1-53（IMD1-53）对心肌损伤的保护作用。方法用ISO建立大鼠缺血损伤模型，观察IMD1-53对心脏功能和心肌组织损伤影响；半定量RT—PCR检测心室肌降钙素受体样受体（calcitonin receptorlike receptor，CL）、受体活性修饰蛋白（receptor—activity—modifying protein，RAMP）1／2／3的mRNA表达水平；放射免疫法测定心肌cAMP的含量和放射配基法测定心肌浆膜IMD受体结合位点。结果与对照组比较ISO组大鼠的左室内压变化速率（±LVdp／dtmax）分别降低23％和44％（均P〈0.01），左室舒张末压（1eft ventricular end—diastolic pressure，LVEDP）增高7，8倍（P〈0.01），心室肌CL、RAMP1／2／3的mRNA水平均明显上调（除RAMP2P〈0.05，均P〈0.01），ISO组心肌浆膜IMD受体Bmax值升高118％[（83.05±5.75）掷（38．10±1．85）pmol·g^-1Pro，P〈0．01]；与单纯ISO组比较，IMD可呈剂量依赖性减轻心内膜下心肌缺血损伤，改善心功能，高剂量Intermedin治疗组大鼠优于低剂量组。结论ISO诱导的缺血损伤心肌的IMD受体上调，而IMD1-53，对心肌缺血损伤具有明显的保护作用。

英文摘要：

Aim cute myocardial Observe the effects of IMD1-53 on ainjury induced by isoproterenol （ISO）. Methods Myocardial ischemia injury in rats was induced by subcutaneous injection with ISO （50 mg · kg^-1 · d^-1, 2days ）, and the therapeutic effect of IMD1-53 was observed. Cardiac function was measured. Myocardial cAMP content was determined by radioimmunoassay （RIA）. The gene expression of calcitonin receptor-like receptor （CL） and receptor-activity-modifying protein （RAMP1） , RAMP2 and RAMP3 in ventricular was determined by semi-quantitative RT-PCR analysis. IMD receptors in cardiac sarcolemmal membrane fractions were assayed [ ^125I ]-IMD binding studies. Results ISO-treated rats showed lower maximal rate of increase and decrease of left-ventricle pressure development （ ± LVdp/dtmax ） and higher left-ventricle end-diastolic pressure （LVEDP; all P 〈 0. 01 ） , which suggested severe heart failure and myocardial injury. Semi-quantitative RT-PCR analysis showed that the gene expression of CL and RAMP1, RAMP2 and RAMP3 in ventricular myocardia were up-regulated by 77% （P〈0.01）, 48% （P〈0.01）, 31% （P〈 0.05） and 130% （P 〈0.01）, respectively, compared with controls. In myocardial sarcolemmal membranes, the maximum binding capacity for [ ^125I ]- IMD1-53 was increased by 118% （P 〈 0.01） in the ISO group compared with controls. Rats treated with low-dosage IMD1-53 （5 nmol · kg^-1· d^-1,2 days） showed significantly higher myocardial cAMP content, by 21% （P〈0.05）, 18% and31% higher ＋LVdp/ dtmax and - LVdp/dtmax respectively, 74% lower LV- EDP （ all P 〈 0. 01 ）, and attenuated myocardial LDH leakage and MDA formation （ all P 〈 0. 01 ）. Treatment with high-dosage IMD1-53（20 nmol · kg^-1 · d^-1, 2 days ） gave better results than with low-dosage IMD1-53. Conclusion These results suggest that the IMD receptor system is up-regulated in ISO-induced myocardial ischemic injury and IMD1-53 may play a pivotal cardioprotective role in such injur