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目的探讨过氧化物酶体增殖物激活受体α(PPARα)配体非诺贝特对心肌梗死后大鼠心肌能量代谢的影响。方法采用开胸结扎冠脉左前降支建立心肌梗死模型,取术后72h存活的20只大鼠随机分为手术组(MI组,n=10)和非诺贝特干预组[F组,n=10,非诺贝特30mg/(kg.d),灌胃8周],另设一假手术组(SH组,n=10)。分别喂养8周后用逆转录聚合酶链式反应(RT-PCR)法检测PPARα,α/β-MHC(肌球蛋白重链同工酶)mRNA的表达。用生物组织氧耗测量仪测定线粒体氧化呼吸活性,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腺苷酸转运体(ANT)转运活性,并经颈动脉插管测定血流动力学指标。结果与SH组比较,MI组PPARαmRNA表达、α/β-MHC明显下调(P<0.01),线粒体内高能磷酸盐含量、呼吸活性、ANT转运活性明显降低(P<0.01),血流动力学指标紊乱(P<0.01);与MI组比较,非诺贝特长期干预升高PPARαmRNA表达(P<0.05),逆转α/β-MHC下调(P<0.05);线粒体内高能磷酸盐含量则未发现有显著变化(P>0.05),但其可改善心肌梗死后心力衰竭大鼠线粒体呼吸活性及ANT转运活性(P<0.05),对血流动力学指标也有改善作用。结论心肌梗死后心力衰竭过程中伴随心肌能量代谢的“胚胎再演”;非诺贝特活化PPARα后可改善心肌能量代谢,延缓心力衰竭的发展,对缺血后心肌有保护作用。
Objective To investigate the effect of fenofibrate, a ligand of peroxisome proliferator-activated receptor α (PPARα), on myocardial energy metabolism in rats after myocardial infarction. Methods The left anterior descending branch of thoracotomy was used to establish the model of myocardial infarction. Twenty rats survived at 72 hours after operation were randomly divided into operation group (MI group, n = 10) and fenofibrate intervention group [group F = 10, fenofibrate 30mg / (kg.d), gavage for 8 weeks], another sham operation group (SH group, n = 10). The mRNA expression of PPARα and α / β-MHC (myosin heavy chain isoenzyme) were detected by reverse transcription polymerase chain reaction (RT-PCR) after feeding for 8 weeks. The mitochondrial oxidative respiration activity was measured by a biological tissue oxygen consumption meter and the mitochondrial adenylate content was measured by high performance liquid chromatography (HPLC). The mitochondrial adenylyl acid (3H-ADP) Transporter (ANT) transport activity, and hemodynamics measured by carotid artery cannulation. Results Compared with SH group, the expression of PPARα mRNA and α / β-MHC in MI group were significantly decreased (P <0.01), and the content of high-energy phosphate, respiration and ANT in mitochondria were significantly decreased (P <0.01). Compared with MI group, long-term fenofibrate treatment increased PPARαmRNA expression (P <0.05) and reversed α / β-MHC downregulation (P <0.05) (P> 0.05). However, it could improve mitochondrial respiration activity and ANT transport activity (P <0.05) and improve hemodynamics in heart failure rats after myocardial infarction. Conclusions The “embryo reemergence” with myocardial energy metabolism during heart failure after myocardial infarction can be improved. Activation of PPARα by fenofibrate improves myocardial energy metabolism, delays the development of heart failure, and has protective effect on post-ischemic myocardium.