摘要
目的:探讨过氧化物酶体增殖物活化受体α(PPARα)/过氧化物酶体增殖物激活受体γ辅激活子1α(PGC-1α)信号通路对血管紧张素Ⅱ(AngⅡ)诱导大鼠肥大心肌细胞能量代谢的影响。方法:将原代培养的新生大鼠心肌细胞分为对照组(C组)、AngⅡ刺激组(AngⅡ组)、PPARα激活剂及非诺贝特预处理组,即(AngⅡ+F)组,C组予生理盐水处理,AngⅡ组加入AngⅡ(终浓度10 mmol/L)刺激24 h建立肥厚心肌细胞模型,(AngⅡ+F)组心肌细胞在AngⅡ刺激前24 h加非诺贝特(l0μmol/L)预处理;HE染色后采用软件检测细胞表面积,用Western-blot检测心肌细胞中PPARα、PGC-1α和腺苷酸转运体(ANT)蛋白表达水平,用高效液相层析法(HPLC)测量线粒体内腺苷酸含量,氚标记二磷酸腺苷(3H-ADP)掺入法检测线粒体膜ANT转运活性。结果:与AngⅡ组相比,非诺贝特可使PGC-1α、ANT表达上调(P<0.05),细胞内线粒体内高能磷酸盐含量则未发现有显著变化(P>0.05),但显著逆转了AngⅡ诱导的心肌细胞肥大,改善了AngⅡ引起的ANT转运活性下降(P<0.05)。结论:PPARα/PGC-1α信号通路激活能有效预防心肌细胞肥大,可改善心肌能量代谢,对缺血后心肌有保护作用。
Objective： To investigate the effects of peroxisome proliferator-activated receptor a （PPARa） and peroxisome proliferator-activated receptor-~/ coactivator （PGC）-lot signal pathway on energy metabolism of angiotensin II （Ang ]1 ） induced hypertrophic cardiomyocytes. Methods： Car- diomyocytes of neonatal rat were divided into control group （group C ）, angiotensin lI stimulating group （ group Ang I[ ） and fenofibrate （ PPARa activator） pretreated group （ group Ang II ＋ F）. Group C was treated with normal saline. Group Ang 11 was given Ang 11 （terminal concentration： 10 mmol/L） for 24 h to establish hypertrophic cardiomyocyte model. Group Ang ]l ＋ F was pretreated with fenofibrate before using Ang 11. After HE staining, the surface area of cardiac myocytes was ana- lyzed with image software. PPARa, PGC-1 a and adenine nucleotide translocator （ANT） protein levels were determined with Western blotting. The content of adenine nucleotide pools were measured by high performance liquid chromatography （HPLC）, and the ANT activity was measured with adenosine diphosphate （3H-ADP） incorporation technique. Results： The protein expression levels of PCG-la and ANT in group Ang ff ＋ F were higher than those in group Ang II, but no significant difference was found in high-energy phosphate （HEP） content in mitochondria （ P 〉 0.05 ）. However, fenofibrate significantly reversed hypertrophy of cardiac myocytes induced by Ang and improved ANT activity. Conclusions： The PPARoJPGC-1 cL signal axis activation can effectively prevent hypertrophy of cardio- myocytes, improve myocardial energy metabolism and have protective effects tn eArrlinrnvnavt~
出处
《贵阳医学院学报》
CAS
2013年第6期607-611,共5页
Journal of Guiyang Medical College
基金
贵州省科学技术基金项目[黔科合J字(2008)2298号]
中国科学院"西部之光"人才培养计划(科发教字[2008]24号)
