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目的研究过氧化物酶体增殖物激活受体α(PPAR-α)对内皮素1诱导的心肌肥大的作用及其对蛋白激酶B/糖原合成酶激酶3β-活化T细胞核因子(Akt/GSK3β-NFATc4)信号通路的影响。方法培养新生SD大鼠的心肌细胞,构建PPAR-α-EGFPN3质粒并转染心肌细胞,采用[3H]亮氨酸掺入法、蛋白免疫印迹(Westernblot)技术、免疫荧光技术等方法,观察PPAR-α过表达对内皮素1诱导的心肌细胞蛋白质合成的作用以及PPAR-α过表达对内皮素1诱导的Akt/GSK3β磷酸化和NFATc4核移位的影响。结果PPAR-α过表达和PPAR-α激动剂非诺贝特显著抑制了内皮素1诱导的心肌肥大;PPAR-α过表达及PPAR-α过表达联用非诺贝特可以显著抑制内皮素1诱导的Akt/GSK3β磷酸化;PPAR-α过表达防止了内皮素1诱导的NFATc4由胞浆到胞核的移位。结论PPAR-α可能通过影响Akt/GSK3β-NFATc4信号通路来抑制内皮素1诱导的心肌肥大反应。
Objective To investigate the effect of peroxisome proliferator - activated receptor α (PPAR - α) on endothelin - 1 - induced cardiac hypertrophy and its effect on the expression of protein kinase B / glycogen synthase kinase 3β - activated T cell nuclear factor (Akt / GSK3β -NFATc4) signaling pathway. Methods Cardiomyocytes of neonatal SD rats were cultured and the PPAR-α-EGFPN3 plasmids were constructed and transfected into cardiomyocytes. [3H] leucine incorporation, Western blot and immunofluorescence techniques were used to observe the changes of PPAR- -α over-expression on endothelin-1-induced cardiomyocyte protein synthesis and the effect of PPAR-α overexpression on endothelin-1-induced Akt / GSK3β phosphorylation and NFATc4 nuclear translocation. Results PPAR-α overexpression and PPAR-α agonist fenofibrate significantly inhibited endothelin-1-induced cardiac hypertrophy; PPAR-α overexpression and PPAR-α overexpression combined with fenofibrate significantly inhibited endothelin 1 Induced Akt / GSK3β phosphorylation; PPAR-α overexpression prevented endothelin-1-induced translocation of NFATc4 from cytoplasm to nucleus. Conclusion PPAR-α may inhibit endothelin-1-induced cardiac hypertrophy by affecting the Akt / GSK3β-NFATc4 signaling pathway.