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2型糖尿病患者中miR-33a、miR-122、红细胞膜脂肪酸谱及血脂与代谢综合征各组分之间关系的研究

Investigation of the relationship between miR-33a, miR-122, erythrocyte membrane fatty acids profile, and serum lipids with components of metabolic syndrome in type 2 diabetic patients.

作者信息

Masoudi Fatemeh, Sharifi Mohammad Reza, Pourfarzam Morteza

机构信息

Department of Clinical Biochemistry and Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

出版信息

Res Pharm Sci. 2022 Apr 18;17(3):242-251. doi: 10.4103/1735-5362.343078. eCollection 2022 Jun.

Abstract

BACKGROUND AND PURPOSE

MicroRNAs (miRNAs) are small non-coding RNA molecules acting as critical regulators of post-transcriptional gene expression. MiR-33a and miR-122 have a crucial role in cholesterol and lipid metabolism. Therefore, their dysregulation may contribute to metabolic abnormality and their inhibition may be a useful therapeutic strategy. The objective of the present study was to investigate the relationship between miR-33a, miR-122, erythrocyte membrane fatty acids profile, and serum lipids with components of metabolic syndrome in an Iranian population suffering from type 2 diabetes mellitus (T2DM).

EXPERIMENTAL APPROACH

Expression of miR-33a and miR-122 was measured by real-time polymerase chain reaction and erythrocyte membrane fatty acid profiles were analyzed by gas chromatography-mass spectrometry.

FINDINGS/RESULTS: T2DM patients with and without metabolic syndrome had significantly higher miR-33a and miR-122 levels compared to controls. MiRNAs were significantly correlated with saturated fatty acid (SFAs), total SFAs/total polyunsaturated fatty acids (PUFAs) ratio, fasting plasma glucose, triacylglycerols, insulin and homeostatic model assessment of insulin resistance. In addition, there was a significant negative correlation between miR-33a and miR-122 levels and PUFAs, total PUFAs/total SFAs ratio and omega 6 fatty acids.

CONCLUSION AND IMPLICATIONS

Considering the roles of miR-33a and miR-122 in cholesterol and lipids metabolism, it may be concluded that the measurement of their expression may be useful as a potential additional biomarker for cardiometabolic derangement in T2DM patients. In addition, these findings may suggest that the inhibition of these miRNAs by anti-miRNA therapies may be explored as a potential therapeutic strategy.

摘要

背景与目的

微小RNA(miRNA)是一类小型非编码RNA分子,在转录后基因表达中起关键调节作用。MiR-33a和miR-122在胆固醇和脂质代谢中起关键作用。因此,它们的失调可能导致代谢异常,抑制它们可能是一种有用的治疗策略。本研究的目的是在患有2型糖尿病(T2DM)的伊朗人群中,研究miR-33a、miR-122、红细胞膜脂肪酸谱和血脂与代谢综合征各组分之间的关系。

实验方法

通过实时聚合酶链反应测量miR-33a和miR-122的表达,并通过气相色谱-质谱法分析红细胞膜脂肪酸谱。

研究结果

与对照组相比,患有和未患有代谢综合征的T2DM患者的miR-33a和miR-122水平显著更高。微小RNA与饱和脂肪酸(SFA)、总SFA/总多不饱和脂肪酸(PUFA)比值、空腹血糖、三酰甘油、胰岛素及胰岛素抵抗稳态模型评估显著相关。此外,miR-33a和miR-122水平与PUFA、总PUFA/总SFA比值和ω-6脂肪酸之间存在显著负相关。

结论与意义

考虑到miR-33a和miR-122在胆固醇和脂质代谢中的作用,可以得出结论,测量它们的表达可能作为T2DM患者心脏代谢紊乱的潜在附加生物标志物。此外,这些发现可能表明,通过抗miRNA疗法抑制这些微小RNA可作为一种潜在的治疗策略进行探索。

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