压力负荷诱导的大鼠肥厚心肌中线粒体形态与Mfn2表达的变化

The alterations of mitochondria morphology and expression of Mfn2 in rats with pressure-overload induced cardiac hypertrophy

目的探讨压力负荷诱导的大鼠肥厚心肌中线粒体形态改变及线粒体融合蛋白2(Mfn2)表达的动态变化。方法采用腹主动脉缩窄法制备压力超负荷大鼠心肌肥厚模型;之后应用多道生理仪检测血流动力学变化,通过透射电镜观察不同时相点心肌细胞线粒体数量及形态变化,并采用分子生物学手段测定Mfn2基因及蛋白表达水平。结果腹主动脉缩窄术后4周大鼠心肌出现肥厚,左心室质量指数(LVW/BW)从(2.38±1.27)mg/g增加到(2.80±1.41)mg/g,伴有明显的血流动力学异常,平均动脉压(MAP)从(104±12.6)mm Hg上升到(184±15.4)mm Hg,左心室收缩压从(94.3±9.4)mm Hg上升到(105.1±11.0)mm Hg,左心室最大压力下降速率则从(4 134±103)mm Hg/s降低到(3 713±114)mm Hg/s。肥厚心肌早期线粒体数量先有短暂的增多,后期数目减少、融合增加、体积增大呈圆形;心肌Mfn2表达下降。结论主动脉缩窄诱导的压力超负荷肥厚心肌中,Mfn2表达逐渐降低,同时线粒体形态及数量出现动态变化,提示Mfn2参与心肌肥厚的发生发展。

ObjectiveThe study was designed to investigate the alteration of mitochondria morphology and expression of Mfn2 in rats with pressure-overload induced cardiac hypertrophy. Methods The cardiac hypertrophy model was established by abdominal aortic constriction （CAA）. Polygraph was used to determine hemodynamics parameters. The mitochondria morphology was observed with transmission electron microscope, and mitofusin 2 （Mfn2） expression level in heart was measured with real-time PCR and Western blot.Results The hemodynamics including mean arterial pressure （MAP） increased from 104 to 184, left ventricular mass index （LVMI） from 2.38 mg/g to 2.80 mg/g, left ventricular systolic pressure （LVSP） were significantly added from 94.3 mmHg to 105.1 mmHg, and the rate of pressure decay （-dp/dt max） was obviously reduced from 4 134 mmHg/s to 3 713 mmHg/s in CAA rats, compared with those in sham rats. In CAA rat heart, the number of mitochondria was initially increased, and then significantly decreased at 16 weeks; and the mitochondria shape was larger due to its fusion. The mRNA and protein expression levels of Mfn2 were significantly down-regulated in CAA group in a time-dependent manner.ConclusionOur data showed that the alterations of mitochondria morphology and expression of Mfn2 were accompanied with the progress of cardiac hypertrophy in CAA rats, which suggesting that Mfn2 may play an important role in progression of cardiac hypertrophy and mitochondrial dynamics.