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添加乳脂肪球膜可促进低出生体重小鼠的生长并减轻脂多糖处理引起的炎症。

Milk Fat Globule Membrane Supplementation Promotes Neonatal Growth and Alleviates Inflammation in Low-Birth-Weight Mice Treated with Lipopolysaccharide.

机构信息

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

Department of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing 100029, China.

出版信息

Biomed Res Int. 2019 May 2;2019:4876078. doi: 10.1155/2019/4876078. eCollection 2019.

Abstract

Impaired intestinal mucosal integrity and immunity are frequently observed in low-birth-weight (LBW) animals, which lead to inadequate growth and high neonatal mortality. However, the mechanisms of intestinal dysfunction in LBW animals are still unclear. Milk fat globule membrane (MFGM), a protein-lipid complex surrounding the fat globules in milk, has many healthful benefits for animals. Therefore, this study was conducted to explore the effect of MFGM supplementation on intestinal injury and inflammation in LBW mouse pups while being challenged with lipopolysaccharide (LPS). C57BL/6J LBW female neonatal mice were fed on breast milk and divided into four groups, including two normal diet groups (ND; CON group and LPS group) and the diet supplemented with two dosages of MFGM, namely, MFGM100 (ND plus MFGM at 100 mg/kg BW) and MFGM200 (ND plus MFGM at 200 mg/kg BW) from postnatal day (PND) 4 to PND 21. At PND21, pups from the LPS group, MFGM100 group, and MFGM200 group were injected intraperitoneally with LPS while the pups from the CON group were injected with equivalent volume of sterile saline. After 4 h of LPS administration, all pups were slaughtered and then the plasma, mid-ileum, and mid-colon tissue samples were collected. Our results showed that MFGM supplementation promoted the body weight from PND16 to PND21 and attenuated intestinal inflammation manifested by reduced histological damage, decreased secretion of TNF-, IL-6, IFN-, and IL-1, and improved oxidative stress characterized by increased SOD activity and decreased secretion of MDA. Expression of tight junction proteins (ZO-1, occludin, and claudin-1), MUC1, and MUC2 was increased in MFGM presupplemented groups compared to the LPS-challenged mice with normal diet. Meanwhile, the expression of proinflammatory cytokines and TLRs was decreased by MFGM presupplementation. Collectively, MFGM is a critical nutrient with an ability to improve the growth performance of LBW mouse pups, especially during the LPS challenge, by promoting the intestinal epithelial integrity and inhibiting inflammation through activating of TLR2 and TLR4 signals.

摘要

低出生体重(LBW)动物常出现肠道黏膜完整性和免疫受损,导致生长不良和新生儿死亡率高。然而,LBW 动物肠道功能障碍的机制尚不清楚。乳脂肪球膜(MFGM)是一种环绕牛奶中脂肪球的蛋白质-脂质复合物,对动物有许多健康益处。因此,本研究旨在探讨 MFGM 补充对 LPS 挑战的 LBW 仔鼠肠道损伤和炎症的影响。C57BL/6J LBW 雌性新生仔鼠用母乳喂养,并分为四组,包括两组正常饮食组(ND;CON 组和 LPS 组)和两组添加 MFGM 剂量的饮食组,即 MFGM100(ND 加 MFGM100mg/kgBW)和 MFGM200(ND 加 MFGM200mg/kgBW),从出生后第 4 天(PND)至 PND21。在 PND21 时,LPS 组、MFGM100 组和 MFGM200 组的仔鼠腹腔内注射 LPS,而 CON 组的仔鼠注射等量无菌生理盐水。LPS 给药 4 小时后,所有仔鼠被屠宰,然后采集血浆、回肠中段和结肠中段组织样本。结果显示,MFGM 补充促进了 PND16 至 PND21 的体重增长,并减轻了肠道炎症,表现为组织损伤减轻、TNF-α、IL-6、IFN-γ和 IL-1 分泌减少,以及氧化应激改善,表现为 SOD 活性增加和 MDA 分泌减少。与正常饮食的 LPS 攻雏组相比,MFGM 预补充组的紧密连接蛋白(ZO-1、occludin 和 claudin-1)、MUC1 和 MUC2 的表达增加。同时,MFGM 预补充降低了促炎细胞因子和 TLRs 的表达。综上所述,MFGM 是一种关键营养素,通过激活 TLR2 和 TLR4 信号,能够改善 LBW 仔鼠的生长性能,尤其是在 LPS 挑战时,通过促进肠道上皮完整性和抑制炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/6521396/42c5848fc039/BMRI2019-4876078.001.jpg

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