摘要
目的:研究过氧化物酶体增殖物激活受体-α(PPAR-α)对心肌细胞肥大的调控作用及其与PI3K/Akt/m TOR通路的关系。方法:异丙肾上腺素(ISO)诱导心肌细胞肥大;Leica图像分析软件测量心肌细胞表面积;qRT-PCR方法检测心房钠尿肽(ANP)、β-肌球蛋白重链(β-MHC)、PPAR-αmRNA表达;Western blot检测Akt、哺乳动物雷帕霉素靶蛋白(m TOR)、P70S6K蛋白表达;PPAR-αRNAi抑制PPAR-α的表达。结果:1心肌细胞肥大时,PPAR-α表达显著下降;非诺贝特(Feno)可上调PPAR-α表达,抑制心肌细胞肥大;Feno对心肌细胞肥大的抑制效应可被PPAR-αRNAi所逆转;2Feno能明显抑制ISO诱导的心肌细胞p-Akt、p-m TOR和p-p70S6K蛋白表达的增加;Feno的上述作用可被PPAR-αRNAi所逆转;3PI3K抑制剂LY294002(LY)或m TOR抑制剂雷帕霉素(RAPA)均能明显抑制心肌细胞肥大,LY或RAPA抑制心肌细胞肥大的效应均可被PPAR-αRNAi所取消。结论:PPAR-α通过负性调控抑制心肌细胞肥大。PPAR-α抑制心肌细胞肥大的作用可能与其抑制PI3K/Akt/m TOR信号通路有关。
Objective： To investigate the effect of perexisiome prohferator activated receptor-a（PPAR-a） on the regulation of cardiomy- ocyte hypertrophy and the relationship between the effect of PPAR-a with PI3K/Akt//mTOR signal pathway. Methods： Cardiomyocyte hyper- trophy was induced by isoproterenol （ISO）. The cell surface area was measured by image analysis system （Leica）. The expressions of atrial natriuretic peptide （ANP） , β-myosin heavy chain（β-MHC） and PPAR-a rnRNA were detected by qRT-PCR. The protein expressions of Akt, roTOR and P70S6K were detected by Western blot. The expression of PPAR-a was suppressed by RNAi. Resttlts： ①The expression of PPAR- a was significantly reduced in cardiomyocyte hyperophy. PPAR-a activator Fenofibrate （Feno） increased the expression of PPAR-a and sup- pressed cardiomyocyte hypertrophy. The inhibitory effect of Feno on cardiomyocyte hypertrophy was reversed by PPAR-a RNAi. ②Feno signifi- cantly inhibited the increase of the protein expressions of p-Akt, p-mTOR and p-p770S6K in ISO induced cardiomyocyte hypertrophy, which could be blocked by PPAR-a RNAi. ③PI3K antagonist LY294002 （LY） or roTOR antagonist rapamycin （RAPA） markedly inhibited car- diomyocyte hypertrophy. The inhibitory effects of LY or RAPA on cardiomyocyte hypertrophy were reversed by PPAR-a RNAi. Conclusion： PPAR-a can negatively regulate eardiomyocyte hypertrophy. The effect might be associated with PPAR-a inhiting PI3K/ Akt/mTOR signal pathway.
出处
《中国应用生理学杂志》
CAS
CSCD
2015年第3期284-288,共5页
Chinese Journal of Applied Physiology
