Echinacoside promotes mitochondrial biosynthesis and inhibition of myocardial apoptosis by up-regulating the PGC-1/NFR signaling pathway / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To investigate the effects of echinacoside （ECH） on mitochondrial biosynthesis and cardiomyocytes’ apoptosis in heart failure （HF） and to explore its related mechanisms. 【Methods】 The experimental animals were divided into three groups： the rat model of HF （HF） was induced by intraperitoneal injection of ISO， and pre-treated with ECH by intraperitoneal injection （ECH） and nomal control （ctrl group）. Cardiac function was detected by echocardiography after 2 weeks of treatment. The ultrastructure of myocardium was observed by transmission electron microscopy and the mitochondrial density and vacuolation rate were analyzed. The expressions of apoptosis-associated proteins were evaluated by Western blotting， and genes related to mitochondrial biosynthesis were examined by Real-time PCR. 【Results】 ECH increased 1eft ventricular ejection fraction （LVEF） and 1eft ventricular fraction shortening （LVFS）， but decreased 1eft ventricular end-systolic diameter （LVEDs） and 1eft ventrieular end-diastolic diameter （LVEDd） when compared to HF group （P<0.01） and improved cardiac function. The myocardial ultrastructure was significantly improved by ECH， the density of regular shapes of mitochondria was increased， and the percentage of vacuolated rate was reduced by ECH （P<0.01）. The expression of anti-apoptotic protein Bcl-2 was upregulated and that of pro-apoptotic protein Bax was downregulated in ECH group. The mRNA of mitochondrial biosynthesis related genes PGC-1， NFR-1， NFR-2 and TFAM was significantly upregulated in ECH group. 【Conclusion】 ECH promotes mitochondrial biosynthesis and inhibits cardiomyocytes’ apoptosis by up-regulating PGC-1/NFR signaling pathway， thus improving cardiac function.