中文摘要：

【目的】研究5-氨基-4甲酰胺咪唑核糖核苷酸（AICAR）对心肌细胞转录因子FOXO3a的活性以及泛素连接酶MAFbx蛋白表达的影响,探讨AMP激活的蛋白激酶（AMPK）在心肌细胞蛋白质降解中所起的作用。【方法】用不同浓度AICAR干预培养的新生大鼠心肌细胞6h,观察AICAR对心肌细胞AMPK的激活作用。再将培养的心肌细胞分成3组：对照组,AICAR组,AICAR＋CompoundC组。用Western blot检测AMPK激活对心肌细胞FOXO3a转录因子活性,以及MAFbx蛋白表达的影响。【结果】①与对照组比较,0.25mmol/L与0.5mmol/LAICAR处理6h后心肌细胞AMPK活性升高（P〈0.05）,而1.0mmol/L与2.0mmol/LAICAR组AMPK活性增加更明显（P〈0.01）。②与对照组比较,AICAR激活AMPK后显著增加FOXO3a转录活性（P〈0.01）,促进MAFbx蛋白表达（P〈0.01）,而特异性的AMPK抑制剂Compound C则明显抑制了该作用。【结论】AMPK可能通过激活心肌细胞FOXO3a的转录活性,上调MAFbx蛋白表达,参与心肌细胞蛋白质降解的调控。

英文摘要：

【Objective】 This study was designed to investigate the effects of 5-aminoimidazole-4-carboxamide ribonucleoside （AICAR） on activity of transcription factor Forkhead O 3a （FOXO3a） and expression of ubiquitin ligase muscle atrophy F-box （MAFbx）, and to explore the role of adenosine monophosphate-activated protein kinase （AMPK） on proteolysis pathways in cardiomyocytes. 【Methods】 The effect of AICAR on activation of AMPK was observed. Cultured neonatal rat cardiomyocytes was treated with AICAR in different concentration. Cultured cardiomyocytes were then divided into three groups： control group, AICAR group, AICAR ＋ Compound C group. Effects of AMPK activation on phosphorylation of FOXO3a and expression of MAFbx in cardiomyocytes were detected using Western blot. 【Results】 ① Compared with control group, activity of AMPK in cultured cardiomyocytes was increased after treatment with 0.25 mmol / L or 0.5 mmol / L AICAR for 6 h （P 0.05）, and the activity of AMPK was further enhanced after treatment with 1.0 mmol / L or 2.0 mmol / L AICAR for 6 h （P〈0.01）. ② Activation of AMPK by AICAR significantly increased the transcriptional activity of FOXO3a （P〈0.01）, and enhanced MAFbx protein expression in cardiomyocytes when comparing with control group （P〈0.01）, however, specific AMPK antagonist Compound C markedly reversed these effects induced by AICAR. 【Conclusion】 AMPK may regulate cardiomyocytes proteolysis by activation of FOXO3a transcription factor, and up-regulation of MAFbx protein expression.