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补充二十二碳六烯酸对2型糖尿病患者血管功能、外周血单个核细胞端粒酶活性、炎性细胞因子表达及PPARγ-LXRα-ABCA1通路的影响:随机对照临床试验研究方案

Effects of DHA Supplementation on Vascular Function, Telomerase Activity in PBMC, Expression of Inflammatory Cytokines, and PPARγ-LXRα-ABCA1 Pathway in Patients With Type 2 Diabetes Mellitus: Study Protocol for Randomized Controlled Clinical Trial.

作者信息

Toupchian Omid, Sotoudeh Gity, Mansoori Anahita, Djalali Mahmoud, Keshavarz Seyyed Ali, Nasli-Esfahani Ensieh, Alvandi Ehsan, Koohdani Fariba

机构信息

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Acta Med Iran. 2016 Jul;54(7):410-7.

PMID:27424010
Abstract

Docosahexaenoic acid (DHA), as an omega-3 fatty acid, in a natural ligand of peroxisome proliferator-activated receptors (PPARs). Regarding the combinative effects of Nutrigenomics and Nutrigenetics and due to the lack of in vivo studies conducted using natural ligands of PPARs, we aimed to evaluate the effects of DHA supplementation on vascular function, telomerase activity, and PPARγ-LXRα-ABCA1 pathway, in patients with type 2 diabetes mellitus (T2DM), based on the Pro12Ala polymorphism in PPARγ encoding gene. 72 T2DM patients (36 dominant and 36 recessive allele carriers), aged 30-70, with body mass index of 18.5 to 35 kg/m2, will be participated in this double blind randomized controlled trial. In each group, stratification will be performed based on sex and age and participants will be randomly assigned to receive 2.4 g/day DHA or placebo (paraffin) for 8 weeks. PPARγ genotyping will be carried out using PCR-RFLP method; Telomerase activity will be estimated by PCR-ELISA TRAP assay; mRNA expression levels of target genes will be assessed using real time PCR. Serum levels of ADMA, sCD163 and adiponectin, will be measured using ELISA commercial kits. The present study is designed in order to help T2DM patients to modify their health conditions based on their genetic backgrounds, and to recommend the proper food ingredients as the natural agonists for PPARs in order to prevent and treat metabolic abnormalities of the disease.

摘要

二十二碳六烯酸(DHA)作为一种ω-3脂肪酸,是过氧化物酶体增殖物激活受体(PPARs)的天然配体。鉴于营养基因组学和营养遗传学的联合效应,且由于缺乏使用PPARs天然配体进行的体内研究,我们旨在基于PPARγ编码基因中的Pro12Ala多态性,评估补充DHA对2型糖尿病(T2DM)患者血管功能、端粒酶活性和PPARγ-LXRα-ABCA1通路的影响。72名年龄在30至70岁、体重指数为18.5至35kg/m²的T2DM患者(36名显性等位基因携带者和36名隐性等位基因携带者)将参与这项双盲随机对照试验。在每组中,将根据性别和年龄进行分层,参与者将被随机分配接受2.4g/天的DHA或安慰剂(石蜡),为期8周。将使用PCR-RFLP方法进行PPARγ基因分型;通过PCR-ELISA TRAP测定法估计端粒酶活性;使用实时PCR评估靶基因的mRNA表达水平。将使用ELISA商业试剂盒测量血清中不对称二甲基精氨酸(ADMA)、可溶性CD163和脂联素的水平。本研究旨在帮助T2DM患者根据其遗传背景改善健康状况,并推荐合适的食物成分作为PPARs的天然激动剂,以预防和治疗该疾病的代谢异常。

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