Intermedin^(1-53)保护异丙基肾上腺素诱导的心肌损伤  

Protect effect of Intermedin_(1-53) on isoproterenol-induced ischemic injury in rats heart

作　　者：贾月霞[1] 潘春水[2] 耿彬[2] 杨靖辉[2] 赵晶[2] 于芳[2] Helen Gerns OU-YANG Ming YANG Jun 唐朝枢[2,4] 齐永芬[2,4] 

机构地区：[1]宁夏医学院病理生理研究室,宁夏银川750004 [2]北京大学医学部生理与病理生理学系,北京100083 [3]Phoenix Pharmaceutical Ine,530 Harbor Boulevard Belmont, CA,94002, USA [4]北京大学第一医院心血管病研究所,北京100034

出　　处：《中国药理学通报》2005年第12期1454-1459,共6页Chinese Pharmacological Bulletin

基　　金：国家重大基础研究发展规划(973计划)资助项目(NoG2000056905);国家自然科学基金资助项目(No:30470693);宁夏自然科学基金资助项目(NoNZ0542)

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Intermedin153(IMD153)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IMD153对心脏功能和心肌组织损伤影响;半定量RTPCR检测心室肌降钙素受体样受体(calcitoninreceptorlikereceptor,CL)、受体活性修饰蛋白(receptoractivitymodifyingprotein,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(leftventricularenddiastolicpressure,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)vs(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IMD153对心肌缺血损伤具有明显的保护作用。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

关 键 词：INTERMEDIN 异丙肾上腺素 降钙素受体样受体 受体活性修饰蛋白 CAMP 

分 类 号：R-332[医药卫生] R322.11