【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。更多还原

【Abstract】 Aim Observe the effects of IMD_ 1-53 on acute myocardial injury 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 IMD_ 1-53 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/dt_ max) 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]-IMD_ 1-53 was increased by 118% (P< 0.01) in the ISO group compared with controls. Rats treated with low-dosage IMD_ 1-53 (5 nmol·kg -1·d -1,2 days) showed significantly higher myocardial cAMP content, by 21% (P<0.05), 18% and 31% higher +LVdp/dt_ max and -LVdp/dt_ max respectively, 74% lower LVEDP (all P<0.01), and attenuated myocardial LDH leakage and MDA formation (all P<0.01). Treatment with high-dosage IMD_ 1-53 (20 nmol·kg -1·d -1, 2 days) gave better results than with low-dosage IMD_ 1-53. Conclusion These results suggest that the IMD receptor system is up-regulated in ISO-induced myocardial ischemic injury and IMD_ 1-53 may play a pivotal cardioprotective role in such injury.更多还原