不同年龄心力衰竭大鼠心肌细胞线粒体呼吸及微黏度变化

V. Korepanov, T. Rebrova, A. Gorbunov, S. Afanasiev
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引用次数: 0

摘要

高光。老年人群的心力衰竭是一个紧迫的医学和社会问题。线粒体功能障碍是心衰发病的关键环节。在这项研究中,我们已经证明了老龄大鼠线粒体呼吸功能的下降。在这个年龄组,心力衰竭的发展伴随着呼吸控制的进一步下降。老年动物线粒体微粘度的增加可能影响心力衰竭时呼吸链酶的活性。研究不同年龄心力衰竭大鼠心肌细胞呼吸活性及线粒体膜微粘度的变化。这项研究涉及22只2至15个月大的雄性Wistar大鼠。将动物分为4组:两龄完整大鼠2组(n = 12), isadrine心力衰竭模型大鼠2组(n = 10)。采用盐酸异丙肾上腺素(170 mg/kg)两次皮下注射,间隔24小时建立HF模型。采用呼吸控制系数评价线粒体呼吸活性。采用芘基荧光探针在蛋白-脂质和脂质-脂质接触区域的实验系数评价线粒体膜的微粘度。采用非参数Mann-Whitney检验对独立组进行比较统计分析。与幼鼠相比,老年大鼠的线粒体呼吸控制能力有所下降。在HF模型中,年龄间差异增大,但与此同时,在较年轻的大鼠中,HF的发展并不伴随着线粒体呼吸控制的明显变化。在蛋白质-脂质和脂质-脂质相互作用区域,线粒体膜微粘度的年龄依赖性下降被揭示出来。在年轻的大鼠中,HF的发展以蛋白-脂质和脂质-脂质接触区域的微粘度显著增加为特征。在老年大鼠中,病理发展的特点是蛋白-脂质相互作用区域的微粘度显著降低。揭示了心力衰竭大鼠心肌细胞线粒体的多向年龄相关变化。结果表明,与老年大鼠不同,年轻大鼠的线粒体在HF模型中保留了其功能活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cardiomyocyte mitochondrial respiration and microviscosity in rats of different ages in heart failure
Highlights. Heart failure in older age groups is an urgent medical and social issue. Mitochondrial dysfunction is a key link in the pathogenesis of heart failure. In this study we have demonstrated a decrease in mitochondrial respiratory function in old rats. In this age group, the development of heart failure is accompanied by a further decrease in respiratory control. An increase in the mitochondrial microviscosity in older animals may affect the activity of respiratory chain enzymes in heart failure.Aim. To study the respiratory activity and mitochondrial membrane microviscosity of cardiomyocyte of rats of different ages with heart failure.Methods. The study involved 22 2- and 15-month-old male Wistar rats. The animals were divided into 4 groups: 2 groups of intact animals of both ages (n = 12) and 2 groups of rats with isadrine model of heart failure (HF) (n = 10). HF was modeled by two subcutaneous injections of isoproterenol hydrochloride (170 mg/kg) at interval of 24 hours. Mitochondrial respiratory activity was assessed using respiratory control coefficient. The microviscosity of mitochondrial membranes was evaluated by eximerization coefficients of pyrene-based fluorescent probe in areas of protein-lipid and lipid-lipid contact. Comparative statistical analysis of independent groups was performed using the nonparametric Mann-Whitney test.Results. A decrease in mitochondrial respiratory control in older rats was shown in comparison with young animals. In the HF model, inter-age difference increases, but at the same time, in younger rats, the development of HF is not accompanied by significant changes in mitochondrial respiratory control. An age dependent decrease in the microviscosity of mitochondrial membranes in the area of protein-lipid and lipid-lipid interaction was revealed. In younger rats, the development  of HF is characterized by a significant increase in microviscosity in the area of protein-lipid and lipid-lipid contact. In older rats, the development of the pathology is characterized by a significant decrease in microviscosity in the area of protein-lipid interaction.Conclusion. Multidirectional age-related changes in cardiomyocyte mitochondria of rats with heart failure were revealed. It was shown that mitochondria in younger rats retain their functional activity in the HF model unlike older rats.
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