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ω-3 长链多不饱和脂肪酸对杜氏肌营养不良症炎症标志物的潜在治疗影响:一项双盲、对照随机试验。

Potential therapeutic impact of omega-3 long chain-polyunsaturated fatty acids on inflammation markers in Duchenne muscular dystrophy: A double-blind, controlled randomized trial.

机构信息

Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI (CMN-SXXI), Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.

Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI (CMN-SXXI), Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.

出版信息

Clin Nutr. 2018 Dec;37(6 Pt A):1840-1851. doi: 10.1016/j.clnu.2017.09.011. Epub 2017 Sep 23.

DOI:10.1016/j.clnu.2017.09.011
PMID:28987470
Abstract

BACKGROUND & AIMS: Duchenne Muscular Dystrophy (DMD) is the most frequent dystrophy in childhood generated by a deficiency in dystrophin. DMD is a neuromuscular disease and its clinical course comprises chronic inflammation and gradual muscle weakness. Supplementation of omega-3 long chain-Polyunsaturated Fatty Acids (ω-3 long chain-PUFA) reduces inflammatory markers in various disorders. The goal of this research was to analyze the influence of ω-3 long chain-PUFA intake on gene expression and blood inflammatory markers in boys with DMD.

METHODS

In a placebo-controlled, double. Blind, randomized trial, boys with DMD (n = 36) consumed 2.9 g/day of ω-3 long chain-PUFA or sunflower oil as control, in capsules, for a period of 6 months. Blood was analyzed at baseline and at months 1, 2, 3, and 6 of supplementation for expression of inflammatory markers in leukocytes and serum.

RESULTS

There was high adherence to capsule intake (control: 95.3% ± 7.2%, and ω-3 long chain-PUFA: 97.4% ± 3.7% at month 6). Enrichment of EicosaPentaenoic Acid (EPA) and DocosaHexaenoic Acid (DHA) in erythrocytes increased significantly in patients supplemented with ω-3 long chain-PUFA compared with the placebo group during the 6 months of supplementation. Messenger RNA (mRNA) of the Nuclear Factor kappa beta (NF-κB) and its target genes InterLeukin 1 beta (IL-1β) and IL-6 was downregulated significantly (p < 0.05) in leukocytes from DMD boys supplemented with ω-3 long chain-PUFA for 6 months, compared to the placebo group. Omega-3 long chain-PUFA intake decreased the serum IL-1β (-59.5%; p = 0.011) and IL-6 (-54.8%; p = 0.041), and increased the serum IL-10 (99.9%, p < 0.005), in relation to those with placebo treatment.

CONCLUSION

Supplementation with ω-3 long chain-PUFA 2.9 g/day is well-tolerated, has a beneficial reductive effect on proinflammatory markers, and increases an anti-inflammatory marker, indicating that ω-3 long chain-PUFA could have a potential therapeutic impact on chronic inflammation in DMD. This research is registered at clinicaltrials.gov (NCT018264229).

摘要

背景与目的

杜氏肌营养不良症(DMD)是儿童中最常见的肌营养不良症,由肌营养不良蛋白缺乏引起。DMD 是一种神经肌肉疾病,其临床过程包括慢性炎症和逐渐的肌肉无力。ω-3 长链多不饱和脂肪酸(ω-3 LCPUFA)的补充可降低各种疾病中的炎症标志物。本研究旨在分析 DMD 男孩摄入 ω-3 LCPUFA 对基因表达和血液炎症标志物的影响。

方法

在一项安慰剂对照、双盲、随机试验中,36 名 DMD 男孩(n=36)每天服用 2.9g ω-3 LCPUFA 或葵花籽油作为对照,胶囊形式,持续 6 个月。在补充的第 1、2、3、6 个月时,分析血液白细胞和血清中炎症标志物的表达。

结果

胶囊摄入量的依从性很高(对照组:95.3%±7.2%,ω-3 LCPUFA 组:97.4%±3.7%,第 6 个月)。与安慰剂组相比,ω-3 LCPUFA 组患者的红细胞中二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)的富集在 6 个月的补充期间显著增加。与安慰剂组相比,DMD 男孩服用 ω-3 LCPUFA 6 个月后,白细胞核因子 kappa B(NF-κB)及其靶基因白细胞介素 1β(IL-1β)和白细胞介素 6(IL-6)的信使 RNA(mRNA)显著下调(p<0.05)。与安慰剂治疗相比,ω-3 LCPUFA 摄入可降低血清白细胞介素 1β(-59.5%;p=0.011)和白细胞介素 6(-54.8%;p=0.041),增加血清白细胞介素 10(99.9%,p<0.005)。

结论

每天补充 2.9g ω-3 LCPUFA 耐受性良好,对促炎标志物具有有益的降低作用,并增加抗炎标志物,表明 ω-3 LCPUFA 可能对 DMD 的慢性炎症具有潜在的治疗作用。本研究在 clinicaltrials.gov(NCT018264229)注册。

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