ERK1/2/PPARα/SCAD信号途径对生理性和病理性心肌肥大的调控

 目的：研究ERK1/2/PPARα/SCAD（短链脂酰辅酶A脱氢酶）信号途径对生理性和病理性心肌肥大调控的不同机制，探索病理性心肌肥大治疗的新靶点。方法：分别以胰岛素样生长因子1（insulin-like growth factor 1，IGF-1）和苯肾上腺素（phenylephrine，PE）刺激心肌细胞，复制生理性和病理性心肌肥大模型，检测心肌细胞表面积，p-ERK1/2和PPARα蛋白表达变化，SCAD mRNA、蛋白表达和酶活性变化，心肌细胞游离脂肪酸含量变化。结果：与对照组比较，PE和IGF-1刺激后心肌细胞表面积均显著增大。与对照组相比，IGF-1刺激的心肌细胞SCAD mRNA和蛋白表达均上调，酶活性显著增高，游离脂肪酸含量明显减少，且PPARα mRNA和蛋白表达均上调，p-ERK1/2的蛋白表达显著下调；PE刺激的心肌细胞SCAD mRNA和蛋白表达均下调，酶活性显著降低，游离脂肪酸含量明显增加，且PPAR αmRNA和蛋白表达均下调，p-ERK1/2蛋白表达显著上调。结论：p-ERK1/2/PPARα/SCAD在生理性和病理性心肌肥大中呈现出不一致的变化趋势，表明ERK1/2/PPARα/SCAD信号途径对2种不同肌肥大的调控作用不同。SCAD可能作为2种不同心肌肥大的分子标志物及病理性心肌肥大的潜在治疗靶点。

Effects of ERK1/2/PPARα/SCAD signal pathways on physiological cardiac hypertrophy and pathological cardiac hypertrophy

AIM：To investigate the different effects of ERK1/2/PPARα/SCAD (short-chain acyl-CoA dehydrogenase) signal pathways on the cardiac hypertrophy induced by insulin-like growth factors 1 (IGF-1) or phenylephrine (PE). METHODS：The neonatal rat cardiomyocytes induced by IGF-1 were used as the model of physiological cardiac hypertrophy， and those induced by PE were used as the model of pathological cardiac hypertrophy. The surface area of the cardiomyocytes, the expression of p-ERK1/2, PPARα and SCAD, the activity of SCAD and the content of free fatty acid in the cardiomyocytes were measured. RESULTS：Compared with the control cells, the surface area of the cardiomyocytes induced by IGF-1 and PE were both increased. Compared with the controls, the expression of SCAD and PPARα, and the activity of SCAD in the cardiomyocytes induced by IGF-1 were increased, while the expression of p-ERK1/2 was decreased. However, the cardiomyocytes treated with PE showed decreased expression of SCAD and PPARα, decreased activity of SCAD and increased expression of p-ERK1/2. Meanwhile, the decrease in free fatty acid in IGF-1-induced cardiomyocytes and the increase in PE-induced cardiomyocytes indicated that the fatty acid utilization was increased in the cardiomyocytes induced by IGF-1, but decreased in the cardiomyocytes induced by PE. CONCLUSION：The changes of p-ERK1/2, PPARα and SCAD in the cardiac hypertrophy induced by IGF-1 or PE indicate that the effects of ERK1/2/PPARα/SCAD signal pathways are different between physiological cardiac hypertrophy and pathological cardiac hypertrophy, and that SCAD may be a molecular marker of these 2 different cardiac hypertrophies and a potential therapeutic target for pathological cardiac hypertrophy.