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炎症标志物可预测 2 型糖尿病女性的锌转运体基因表达。

Inflammation markers predict zinc transporter gene expression in women with type 2 diabetes mellitus.

机构信息

Discipline of Nutrition and Metabolism, School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.

出版信息

J Nutr Biochem. 2013 Sep;24(9):1655-61. doi: 10.1016/j.jnutbio.2013.02.006. Epub 2013 May 2.

DOI:10.1016/j.jnutbio.2013.02.006
PMID:23643522
Abstract

The pathology of type 2 diabetes mellitus (DM) often is associated with underlying states of conditioned zinc deficiency and chronic inflammation. Zinc and omega-3 polyunsaturated fatty acids each exhibit anti-inflammatory effects and may be of therapeutic benefit in the disease. The present randomized, double-blind, placebo-controlled, 12-week trial was designed to investigate the effects of zinc (40 mg/day) and α-linolenic acid (ALA; 2 g/day flaxseed oil) supplementation on markers of inflammation [interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP)] and zinc transporter and metallothionein gene expression in 48 postmenopausal women with type 2 DM. No significant effects of zinc or ALA supplementation were observed on inflammatory marker concentrations or fold change in zinc transporter and metallothionein gene expression. Significant increases in plasma zinc concentrations were observed over time in the groups supplemented with zinc alone or combined with ALA (P=.007 and P=.009, respectively). An impact of zinc treatment on zinc transporter gene expression was found; ZnT5 was positively correlated with Zip3 mRNA (P<.001) only in participants receiving zinc, while zinc supplementation abolished the relationship between ZnT5 and Zip10. IL-6 predicted the expression levels and CRP predicted the fold change of the ZnT5, ZnT7, Zip1, Zip7 and Zip10 mRNA cluster (P<.001 and P=.031, respectively). Fold change in the expression of metallothionein mRNA was predicted by TNF-α (P=.022). Associations among inflammatory cytokines and zinc transporter and metallothionein gene expression support an interrelationship between zinc homeostasis and inflammation in type 2 DM.

摘要

2 型糖尿病(DM)的病理学常与潜在的条件性锌缺乏和慢性炎症状态有关。锌和欧米伽-3 多不饱和脂肪酸都具有抗炎作用,在该疾病中可能具有治疗益处。本随机、双盲、安慰剂对照、为期 12 周的试验旨在研究锌(40 毫克/天)和α-亚麻酸(ALA;2 克/天亚麻籽油)补充对 48 例 2 型 DM 绝经后妇女炎症标志物[白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、C 反应蛋白(CRP)]和锌转运体和金属硫蛋白基因表达的影响。锌或 ALA 补充对炎症标志物浓度或锌转运体和金属硫蛋白基因表达的倍数变化均无显著影响。仅在单独补充锌或与 ALA 联合补充锌的组中,随着时间的推移,血浆锌浓度显著增加(分别为 P=.007 和 P=.009)。锌治疗对锌转运体基因表达有影响;只有在接受锌治疗的参与者中,ZnT5 与 Zip3 mRNA 呈正相关(P<.001),而锌补充则消除了 ZnT5 与 Zip10 之间的关系。IL-6 预测 ZnT5、ZnT7、Zip1、Zip7 和 Zip10 mRNA 簇的表达水平(P<.001 和 P=.031),CRP 预测 ZnT5、ZnT7、Zip1、Zip7 和 Zip10 mRNA 簇的倍数变化(P<.001 和 P=.031)。金属硫蛋白 mRNA 的倍数变化由 TNF-α预测(P=.022)。炎症细胞因子与锌转运体和金属硫蛋白基因表达之间的关联支持 2 型 DM 中锌稳态与炎症之间的相互关系。

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