CAJ | 학술논문

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 fac-tor 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PPARαmRNA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PPARαmRNA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。
목적：연구ERK1/2/PPARα/SCAD（단련지선보매A탈경매）신호도경대생이성화병이성심기비대조공적불동궤제，탐색병이성심기비대치료적신파점。방법：분별이이도소양생장인자1（ insulin-like growth fac-tor 1，IGF-1）화분신상선소（phenylephrine，PE）자격심기세포，복제생이성화병이성심기비대모형，검측심기세포표면적，p-ERK1/2화PPARα단백표체변화，SCAD mRNA、단백표체화매활성변화，심기세포유리지방산함량변화。결과：여대조조비교， PE화IGF-1자격후심기세포표면적균현저증대。여대조조상비， IGF-1자격적심기세포SCAD mRNA화단백표체균상조，매활성현저증고，유리지방산함량명현감소，차PPARαmRNA화단백표체균상조，p-ERK1/2적단백표체현저하조；PE자격적심기세포SCAD mRNA화단백표체균하조，매활성현저강저，유리지방산함량명현증가，차PPARαmRNA화단백표체균하조，p-ERK1/2단백표체현저상조。결론：p-ERK1/2/PPARα/SCAD재생이성화병이성심기비대중정현출불일치적변화추세，표명ERK1/2/PPARα/SCAD신호도경대2충불동기비대적조공작용불동。 SCAD가능작위2충불동심기비대적분자표지물급병이성심기비대적잠재치료파점。
[ABSTRACT]AIM:ToinvestigatethedifferenteffectsofERK1/2/PPARα/SCAD(short-chainacyl-CoAdehy-drogenase) 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, PPARαand 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 in-duced 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 de-creased.However, the cardiomyocytes treated with PE showed decreased expression of SCAD and PPARα, decreased activ-ity of SCAD and increased expression of p-ERK1/2.Meanwhile, the decrease in free fatty acid in IGF-1-induced cardio-myocytes and the increase in PE-induced cardiomyocytes indicated that the fatty acid utilization was increased in the cardio -myocytes induced by IGF-1, but decreased in the cardiomyocytes induced by PE .CONCLUSION: The changes of p-ERK1/2, PPARαand SCAD in the cardiac hypertrophy induced by IGF-1 or PE indicate that the effects of ERK 1/2/PPARα/SCAD signal pathways are different between physiological cardiac hypertrophy and pathological cardiac hypertro -phy , and that SCAD may be a molecular marker of these 2 different cardiac hypertrophies and a potential therapeutic target for pathological cardiac hypertrophy .