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吡格列酮通过影响细胞内钠离子稳态失调对代谢综合征大鼠发挥有益作用。

Pioglitazone provides beneficial effect in metabolic syndrome rats via affecting intracellular Na Dyshomeostasis.

机构信息

Department of Biophysics, Faculty of Medicine, Ankara Yıldırım Beyazıt University, Ankara, Turkey.

Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Turkey.

出版信息

J Bioenerg Biomembr. 2018 Dec;50(6):437-445. doi: 10.1007/s10863-018-9776-6. Epub 2018 Oct 25.

Abstract

Metabolic syndrome, is associated impaired blood glucose level, insulin resistance, and dyslipidemia caused by abdominal obesity. Also, it is related with cardiovascular risk accumulation and cardiomyopathy. The hypothesis of this study was to examine the effect of thiazolidinediones such as pioglitazone on intracellular Na homeostasis in heart of metabolic syndrome male rats. Abdominal obesity and glucose intolerance had measured as a marker of metabolic syndrome. Intracellular Na concentration ([Na]) at rest and [Na] during pacing with electrical field stimulation were determined in freshly isolated cardiomyocytes. Also, TTX-sensitive Na- channel current (I) density and I-V characteristics of these channels were measured to understand [Na] homeostasis. We determined the protein levels of Na/Ca exchanger and Na-K pump to understand the relation between [Na] homeostasis. High sucrose intake significantly increased body mass and blood glucose level of the rats in the metabolic syndrome group as compared with control group. There was a decrease in I density and there were differences in points on activation curve of I. Basal [Na] in metabolic syndrome group significantly increased but there was a significantly decrease in [Na] in stimulated cardiomyocytes in metabolic syndrome. Furthermore, pioglitazone induced decreases in the basal [Na] and preserved the decrease in I and [Na] in stimulated cardiomyocytes to those of controls. Histologically, metabolic syndrome affected heart and associated tissues together with many other organs. Results of the present study suggest that pioglitazone has significant beneficial effects on metabolic syndrome associated disturbances in the heart via effecting Na homeostasis in cardiomyocytes.

摘要

代谢综合征与血糖水平受损、胰岛素抵抗和腹部肥胖引起的血脂异常有关。此外,它还与心血管风险积累和心肌病有关。本研究的假设是检验噻唑烷二酮类药物(如吡格列酮)对代谢综合征雄性大鼠心肌细胞内钠离子稳态的影响。腹部肥胖和葡萄糖耐量受损被作为代谢综合征的标志物进行测量。在新鲜分离的心肌细胞中,测定静息时和电刺激起搏时的细胞内钠离子浓度([Na])。还测量了 TTX 敏感的钠离子通道电流 (I)密度和这些通道的 I-V 特性,以了解 [Na] 稳态。我们测定了钠/钙交换体和钠-钾泵的蛋白水平,以了解 [Na] 稳态之间的关系。与对照组相比,高蔗糖摄入显著增加了代谢综合征组大鼠的体重和血糖水平。I 密度降低,I 的激活曲线的点有差异。代谢综合征组的基础 [Na] 显著增加,但刺激的心肌细胞中的 [Na] 显著降低。此外,吡格列酮诱导基础 [Na] 降低,并保持刺激的心肌细胞中的 I 和 [Na] 降低至对照组的水平。组织学上,代谢综合征与许多其他器官一起影响心脏和相关组织。本研究结果表明,吡格列酮通过影响心肌细胞中的钠离子稳态,对代谢综合征相关的心脏紊乱具有显著的有益作用。

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