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三种他汀类药物对心肌细胞葡萄糖摄取的影响及其机制

Effect of Three Statins on Glucose Uptake of Cardiomyocytes and its Mechanism.

作者信息

Jiang Zhenhuan, Yu Bo, Li Yang

机构信息

Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).

出版信息

Med Sci Monit. 2016 Aug 11;22:2825-30. doi: 10.12659/msm.897047.

Abstract

BACKGROUND The aim of this study was to investigate the effects of different statins on glucose uptake and to confirm its mechanism in primary cultured rat cardiomyocytes after administration of atorvastatin, pravastatin, and rosuvastatin. MATERIAL AND METHODS Primary cultured rat cardiomyocytes were randomly assigned to 5 groups: normal control group (OB), insulin group (S1), statin 1-μM (S2), 5-μM (S3), and 10-μM (S4) groups for 3 different statins. The 2-[3H]-DG uptake of each group was determined and the mRNA and protein expression levels of glucose transporter type 4 (GLUT4), insulin receptor substrate (IRs), and RhoA were assessed. RESULTS After treatment with different concentrations of statins and insulin, the 2-[3H]-DG uptake showed a significant negative correlation with the concentration of atorvastatin (P<0.05), and no significant correlation with pravastatin and rosuvastatin. The mRNA and protein expression levels of GLUT4 and IRs-1 in primary cultured cardiomyocytes were both significantly reduced by atorvastatin treatment (P<0.05). Pravastatin and rosuvastatin showed no significant effects on GLUT4 and IRs-1 expression. The mRNA and protein expression levels of RhoA both showed no significant difference when treated with the 3 statins. CONCLUSIONS These results confirm that atorvastatin can inhibit insulin-induced glucose uptake in primary cultured rat cardiomyocytes by regulating the PI3K/Akt insulin signal transduction pathway.

摘要

背景 本研究旨在探讨不同他汀类药物对葡萄糖摄取的影响,并在给予阿托伐他汀、普伐他汀和瑞舒伐他汀后,在原代培养的大鼠心肌细胞中证实其作用机制。

材料与方法 原代培养的大鼠心肌细胞随机分为5组:正常对照组(OB)、胰岛素组(S1)、1 μM他汀组(S2)、5 μM他汀组(S3)和10 μM他汀组(S4),用于3种不同的他汀类药物。测定每组的2-[3H]-DG摄取量,并评估葡萄糖转运蛋白4(GLUT4)、胰岛素受体底物(IRs)和RhoA的mRNA和蛋白表达水平。

结果 用不同浓度的他汀类药物和胰岛素处理后,2-[3H]-DG摄取量与阿托伐他汀浓度呈显著负相关(P<0.05),与普伐他汀和瑞舒伐他汀无显著相关性。阿托伐他汀处理显著降低了原代培养心肌细胞中GLUT4和IRs-1的mRNA和蛋白表达水平(P<0.05)。普伐他汀和瑞舒伐他汀对GLUT4和IRs-1表达无显著影响。3种他汀类药物处理后,RhoA的mRNA和蛋白表达水平均无显著差异。

结论 这些结果证实,阿托伐他汀可通过调节PI3K/Akt胰岛素信号转导途径抑制原代培养大鼠心肌细胞中胰岛素诱导的葡萄糖摄取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7415/4984921/98661f15906a/medscimonit-22-2825-g001.jpg

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