中文摘要：

目的：研究异丙肾上腺素心肌病模型心肌细胞肌浆网钙ATP酶（sarco-endoplasmic reticulum ATPase 2a,SERCA2a）表达的改变,以及新型内皮素受体拮抗剂CPU0213的治疗作用。方法：雄性SD大鼠皮下给予异丙肾上腺素（2mg·kg^-1·d^-1）10d,治疗组动物在第6到第10天皮下给予CPU0213（30mg·kg^-1·d^-1）。各组动物颈动脉插管记录心功能指标：左心室收缩压（LVSP）,左心室舒张末期压（LVEDP）,和左心室压力变化最大速率（±dp/dtmax）。左心室心肌组织SERCA2a的mRNA及蛋白表达分别用逆转录聚合酶链反应（RT-PCR）和蛋白免疫印迹法（Western blotting）测定。结果：异丙肾上腺素引起左心室收缩和舒张功能明显下降,同时SERCA2a的mRNA及蛋白表达均显著下调（P〈0.05）。CPU0213显著提高SERCA2a表达（P〈0.05）,明显改善心功能（P〈0.05）。结论：CPU0213可通过逆转肌浆网钙调控蛋白SERCA2a的表达下调,使异丙肾上腺素引起的心功能下降得以恢复。本实验证明SERCA2a是β受体过度激活引发心衰过程中的重要靶点。内皮素受体介导了β受体过度激活状态下SER-CA2a的表达下调,是内皮素受体拮抗剂治疗心衰的重要依据之一。

英文摘要：

AIM： The present study was focused on the effects of isoproteronol induced cardiomyopathy, and the expression of sarcoplasm reticulum Ca^2＋ handling protein, sarco-endoplasmic reticulum ATPase 2a （SERCA2a）. The therapeutic effects of CPU0213, a novel endothelin receptor antagonist were evaluated. METHODS： Male SD rats were administrated isoproteronol （2 mg·kg^-1·d^-1, s.c.） for 10 days. A subset of the rats were administrated CPU0213 （30 mg·kg^-1·d^-1, s.c. ） from d 6 to d 10. All the animals were subjected to cannulation through left carotid artery to measure LVSP, LVEDP, and ± dp/dtmax Expressions of SERCA2a were measured by reverse transcription polymerase chain reaction （ RT-PCR ） and western blotting assays. RESULTS： Isoproteronol caused a significant decline of SERCA2a expression in both mRNA and protein levels （P 〈 0.05）, in conjunction with decreased LVSP,± dp/dtmax, and elevated LVEDP（ P 〈0.05）. And CPU0213 recovered all these alterations partially. CONCLUSION： Blockade of endothelin receptors by CPU0213 is beneficial to isoproteronol caused impairment of cardiac function, in which process endothelin system probably mediates the adverse effects of excessive β-receptor activation.