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生命早期膳食供应二十二碳六烯酸对雌性大鼠后代的免疫发育和口服耐受性的建立至关重要。

A Dietary Supply of Docosahexaenoic Acid Early in Life Is Essential for Immune Development and the Establishment of Oral Tolerance in Female Rat Offspring.

作者信息

Richard Caroline, Lewis Erin D, Goruk Susan, Field Catherine J

机构信息

Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.

Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada

出版信息

J Nutr. 2016 Nov;146(11):2398-2406. doi: 10.3945/jn.116.237149. Epub 2016 Sep 28.

Abstract

BACKGROUND

The early postnatal period is critical for immunity, and feeding docosahexaenoic acid (DHA) has been demonstrated to affect immune development.

OBJECTIVE

The objective of this study was to determine the importance of feeding DHA during suckling and/or weaning on immune function and oral tolerance (OT).

METHODS

Sprague-Dawley rats were randomly assigned to 1 of 2 nutritionally adequate diets throughout lactation (21 d): a control (n = 12, 0% DHA) diet or a DHA (n = 8, 0.9% DHA) diet. At 11 d, suckled pups from each dam were randomly assigned to a mucosal OT challenge: placebo or ovalbumin. At week 5, all pups systemically received ovalbumin + adjuvant to induce systemic immunization. At 21 d, pups from each dam were randomly assigned to 1 of the 2 diets for 21 d in a factorial design after which immune function and OT were assessed.

RESULTS

Feeding dams DHA during lactation resulted in a 40-60% higher splenocyte production of interleukin (IL)-10 when stimulated with concanavalin A, lipopolysaccharide (LPS), or ovalbumin and a 100% higher production of interferon (IFN)-γ with LPS (P < 0.05) than feeding the control diet to the pups. In comparison with pups fed the control diet, feeding DHA at weaning resulted in a 25% lower type 1 T helper (IL-1β) and type 2 T helper (IL-6) response by splenocytes after LPS stimulation and a 33% lower plasma concentration of ovalbumin-specific immunoglobulin (Ig) G (P < 0.05). Pups that did not receive additional DHA during the study had a 70% higher plasma concentration of ovalbumin-specific IgE than did the pups that received DHA at suckling and/or weaning (P < 0.05).

CONCLUSIONS

Feeding additional DHA during suckling had a beneficial programming effect on the ability of immune cells to produce IFN-γ and IL-10, and feeding DHA during weaning resulted in a lower inflammatory response. Providing no dietary DHA in either of the critical periods of immune development prevented the establishment of OT in female rat offspring.

摘要

背景

出生后早期对免疫功能至关重要,已证实喂食二十二碳六烯酸(DHA)会影响免疫发育。

目的

本研究的目的是确定在哺乳和/或断奶期间喂食DHA对免疫功能和口服耐受(OT)的重要性。

方法

在整个哺乳期(21天),将Sprague-Dawley大鼠随机分为2种营养充足的饮食组之一:对照组(n = 12,0%DHA)饮食或DHA组(n = 8,0.9%DHA)饮食。在第11天,将来自每只母鼠的哺乳幼崽随机分配进行黏膜OT挑战:安慰剂或卵清蛋白。在第5周,所有幼崽全身接受卵清蛋白+佐剂以诱导全身免疫。在第21天,将来自每只母鼠的幼崽以析因设计随机分配到2种饮食中的1种,持续21天,之后评估免疫功能和OT。

结果

与给幼崽喂食对照饮食相比,在哺乳期给母鼠喂食DHA,当用伴刀豆球蛋白A、脂多糖(LPS)或卵清蛋白刺激时,脾细胞产生白细胞介素(IL)-10的量高40 - 60%,用LPS刺激时产生干扰素(IFN)-γ的量高100%(P < 0.05)。与喂食对照饮食的幼崽相比,在断奶时喂食DHA导致LPS刺激后脾细胞产生的1型辅助性T细胞(IL-1β)和2型辅助性T细胞(IL-6)反应降低25%,卵清蛋白特异性免疫球蛋白(Ig)G的血浆浓度降低33%(P < 0.05)。在研究期间未接受额外DHA的幼崽,其卵清蛋白特异性IgE的血浆浓度比在哺乳和/或断奶时接受DHA的幼崽高70%(P < 0.05)。

结论

在哺乳期间额外喂食DHA对免疫细胞产生IFN-γ和IL-10的能力具有有益的编程作用,在断奶时喂食DHA导致炎症反应降低。在免疫发育的两个关键时期均不提供膳食DHA会阻止雌性大鼠后代建立OT。

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