松果菊苷通过上调PGC-1/NFR信号通路促进线粒体生物合成抑制心肌细胞凋亡

Echinacoside promotes mitochondrial biosynthesis and inhibition of myocardial apoptosis by up-regulating the PGC-1/NFR signaling pathway

目的探讨松果菊苷(echinacoside,ECH)对心力衰竭心肌细胞线粒体生物合成及心肌细胞凋亡的影响及相关机制。方法实验动物分为3组,HF组为异丙肾上腺素(isoproterenol,ISO)腹腔注射诱导建立心力衰竭大鼠模型组,ECH组为造模同时腹腔注射ECH干预,对照组(Ctrl组)仅腹腔注射生理盐水。2周后超声心动图检测心功能,透射电镜观察心肌超微结构并分析线粒体密度及空泡化率,Western blotting定量检测心肌细胞凋亡相关蛋白表达,Realtime PCR检测线粒体生物合成相关基因的表达。结果ECH组左心室射血分数(1eft ventricular ejection fraction,LVEF)及短轴缩短率(1eft ventricular fraction shortening,LVFS)较HF组升高,左心室收缩末容积(1eft ventricular endsystolic diameter,LVEDs)及左心室舒张末容积(1eft ventrieular end-diastolic diameter,LVEDd)降低(P<0.01),心功能改善;与HF组相比,ECH组心肌超微结构明显改善,形态正常线粒体密度明显增加,空泡化率明显减低(P<0.01);ECH组心肌组织抗凋亡蛋白Bcl-2表达上调,促凋亡蛋白Bax表达降低;ECH组线粒体生物合成相关基因PGC-1、NFR-1、NFR-2、TFAM的mRNA表达明显上调。结论ECH可能通过上调PGC-1/NFR信号通路促进线粒体生物合成,抑制心肌细胞凋亡,进而改善心功能。

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 pretreated 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.