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乳脂肪球膜抑制短肠综合征大鼠模型中 NLRP3 炎性小体的激活并增强肠道屏障功能。

Milk Fat Globule Membrane Inhibits NLRP3 Inflammasome Activation and Enhances Intestinal Barrier Function in a Rat Model of Short Bowel.

机构信息

Department of Clinical Nutrition, Xin Hua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.

出版信息

JPEN J Parenter Enteral Nutr. 2019 Jul;43(5):677-685. doi: 10.1002/jpen.1435. Epub 2018 Aug 24.

Abstract

BACKGROUND

The milk fat globule membrane (MFGM) contains various bioactive components which have been shown to maintain gut barrier integrity. This study aimed to evaluate the protective effects of MFGM on intestinal barrier function and its possible mechanisms in a rat model of short bowel syndrome (SBS).

MATERIALS AND METHODS

Five-week-old male Sprague-Dawley rats were divided into 3 groups (n = 8 per group), consisting of Sham group and rats submitted to massive small-bowel resection then supplemented with either water (SBS) or 1.5g/kg/d MFGM (SBS+MFGM) by daily gavage. Rats were sacrificed on day 15 postoperation. Intestinal adaptation, gut permeability, bacterial translocation (BT), expression of tight junction proteins, mucin 1 (MUC1), and nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) pathway in the ileum were evaluated.

RESULTS

Both SBS+MFGM and SBS groups exhibited lower body weight and higher ileum villus height than Sham group, but no difference was detected between each other. SBS group had significantly higher intestinal permeability and BT rate than other groups (P < .05). Compared with SBS rats, SBS+MFGM group showed higher expression of tight junction proteins and MUC1, lower expression of NLRP3 and caspase-1 in the ileum, as well as lower interleukin (IL)-1β but higher IL-18 levels in ileum tissue.

CONCLUSIONS

Supplementation of MFGM helps to modulate NLRP3 inflammasome activation and enhances gut barrier integrity in rats after massive small-bowel resection, which provides experimental support for potential applications of MGFM in intestinal barrier dysfunction, although further studies are needed.

摘要

背景

牛奶脂肪球膜 (MFGM) 含有多种生物活性成分,已被证明能维持肠道屏障的完整性。本研究旨在评估 MFGM 对短肠综合征 (SBS) 大鼠模型肠道屏障功能的保护作用及其可能的机制。

材料与方法

5 周龄雄性 Sprague-Dawley 大鼠随机分为 3 组(每组 8 只):假手术组(Sham 组)和接受大部分小肠切除术后分别给予水(SBS 组)或 1.5g/kg/d MFGM(SBS+MFGM 组)灌胃的大鼠。术后第 15 天处死大鼠。评估肠道适应性、肠道通透性、细菌易位(BT)、小肠紧密连接蛋白、黏蛋白 1(MUC1)和核苷酸结合寡聚结构域样受体含富含亮氨酸重复序列和pyrin 结构域蛋白 3(NLRP3)通路的表达。

结果

SBS+MFGM 组和 SBS 组大鼠体重较 Sham 组低,空肠绒毛高度较 Sham 组高,但两组间无差异。SBS 组大鼠肠道通透性和 BT 率显著高于其他两组(P<0.05)。与 SBS 组大鼠相比,SBS+MFGM 组大鼠小肠紧密连接蛋白和 MUC1 表达较高,NLRP3 和 caspase-1 表达较低,空肠组织中白细胞介素(IL)-1β水平较低,IL-18 水平较高。

结论

补充 MFGM 有助于调节 NLRP3 炎性小体的激活,增强大鼠小肠广泛切除后肠道屏障的完整性,为 MFGM 在肠道屏障功能障碍中的潜在应用提供了实验支持,尽管还需要进一步的研究。

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