摘要
目的 :研究过氧化物酶体增殖物激活受体α(peroxisome proliferators activated receptor alpha,PPAR-α)对心肌细胞肥大的负性调控作用以及与PI3K/Akt/叉头框蛋白O1(Forkhead box O1,FoxO1)信号通路和氧化应激的关系。方法:应用异丙肾上腺素(isoproternol,ISO)诱导心肌细胞肥大;采用Leica图像分析软件测量心肌细胞表面积;应用实时定量聚合酶链式反应(real time quantitative polymerase chain reaction,q RT-PCR)检测心房利钠肽(atrial natriuretic peptide,ANP)、β-肌球蛋白重链(β-myosin heavy chain,β-MHC)、PPAR-α及FoxO1 mRNA表达;采用试剂盒检测心肌细胞超氧化物歧化酶(superoxide dismutase,SOD)活性和丙二醛(malondialdehyde,MDA)含量。结果:(1)ISO诱导心肌细胞肥大,PPAR-αm RNA表达显著下降。(2)应用非诺贝特(Fenofibrate,Feno)上调PPAR-α表达明显抑制ISO诱导的心肌细胞表面积、ANP和β-MHC mRNA表达的增加。(3)ISO诱导心肌细胞肥大,FoxO1表达明显减少;应用Feno预处理可增加FoxO1 mRNA的表达;应用PI3K抑制剂LY预处理亦能明显增加FoxO1 mRNA表达。(4)ISO诱导心肌细胞肥大,心肌细胞SOD活性明显降低,MDA含量明显增加,应用Feno预处理能显著提高SOD活性,降低MDA含量。结论:PPAR-α抑制心肌细胞肥大的作用可能与其抑制PI3K/Akt通路的激活,提高FoxO1的表达,降低氧化应激反应有关。
Objective： To investigate the negative regulation of peroxisome proliferators activated receptor alpha（PPAR-α） on the cardiomyocyte hypertrophy and the interaction of PPAR-α with PI3K/Akt/Forkhead box O1（FoxO1） signaling pathway and the oxidative stress response. Methods： Isoprenaline（ISO） was applied to induce cardiomyocyte hypertrophy. Cell morphology was imaged by phase-contrast microscopy and cell surface area was measured by Leica image analysis software. The expression of atrial natriuretic peptide（ANP）, β-myosin heavy chain（β-MHC）, PPAR-α, Forkhead box O1（FoxO1） mRNA were assessed by realtime quantitative polymerase chain realtion（q RT-PCR）. The activity of superoxide dismutase（SOD） and malondialdebyde（MDA） were detected to discover the change of oxygen free radical. Results：（1）Cardiomyocyte hypertrophy was induced by isoproterenol. The expression of PPAR-α was significantly reduced in cardiomyocyte hypertrophy.（ 2） Application of Feno upregulated the expression of PPAR-α, which could inhibite cell surface and the expression of ANP, β-MHC m RNA in cardiomyocytes.（3）The expression of FoxO1 was inhibited by ISO. Feno or LY could increase the m RNA expression of FoxO1.（4）ISO could reduce the SOD activity, significantly elevate the expression of MDA. Feno significantly increased SOD activity, decreased the expression of MDA. Conclusion： PPAR-α can inhibit PI3K/Akt signal pathway, elevate the expression of FoxO1 and reduce oxidative stress, resulting in the attenuation of cardiomyocyte hypertrophy.
出处
《南通大学学报（医学版）》
2016年第2期115-119,共5页
Journal of Nantong University(Medical sciences)
