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烟酰胺通过 GPR109A 诱导的水通道蛋白表达上调改善肠道健康。

Niacin Improves Intestinal Health through Up-Regulation of AQPs Expression Induced by GPR109A.

机构信息

State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition, Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China.

出版信息

Int J Mol Sci. 2022 Jul 28;23(15):8332. doi: 10.3390/ijms23158332.

DOI:10.3390/ijms23158332
PMID:35955466
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9368703/
Abstract

(1) Background: Changes in the expression of aquaporins (AQPs) in the intestine are proved to be associated with the attenuation of diarrhea. Diarrhea is a severe problem for postweaning piglets. Therefore, this study aimed to investigate whether niacin could alleviate diarrhea in weaned piglets by regulating AQPs expression and the underlying mechanisms; (2) Methods: 72 weaned piglets (Duroc × (Landrace × Yorkshire), 21 d old, 6.60 ± 0.05 kg) were randomly allotted into 3 groups for a 14-day feeding trial. Each treatment group included 6 replicate pens and each pen included 4 barrows (n = 24/treatment). Piglets were fed a basal diet (CON), a basal diet supplemented with 20.4 mg niacin/kg diet (NA) or the basal diet administered an antagonist for the GPR109A receptor (MPN). Additionally, an established porcine intestinal epithelial cell line (IPEC-J2) was used to investigate the protective effects and underlying mechanism of niacin on AQPs expression after Escherichia coli K88 (ETEC K88) treatment; (3) Results: Piglets fed niacin-supplemented diet had significantly decreased diarrhea rate, and increased mRNA and protein level of ZO-1, AQP 1 and AQP 3 in the colon compared with those administered a fed diet supplemented with an antagonist (p < 0.05). In addition, ETEC K88 treatment significantly reduced the cell viability, cell migration, and mRNA and protein expression of AQP1, AQP3, AQP7, AQP9, AQP11, and GPR109A in IPEC-J2 cells (p < 0.05). However, supplementation with niacin significantly prevented the ETEC K88-induced decline in the cell viability, cell migration, and the expression level of AQPs mRNA and protein in IPEC-J2 cells (p < 0.05). Furthermore, siRNA GPR109A knockdown significantly abrogated the protective effect of niacin on ETEC K88-induced cell damage (p < 0.05); (4) Conclusions: Niacin supplementation increased AQPs and ZO-1 expression to reduce diarrhea and intestinal damage through GPR109A pathway in weaned piglets.

摘要

(1)背景:水通道蛋白(AQPs)在肠道中的表达变化被证明与腹泻的减轻有关。腹泻是断奶仔猪的严重问题。因此,本研究旨在探讨烟酸是否可以通过调节 AQPs 的表达来减轻断奶仔猪的腹泻及其潜在机制;(2)方法:72 头断奶仔猪(杜洛克×(长白×约克夏),21 日龄,6.60±0.05kg)随机分为 3 组进行 14 天的饲养试验。每个处理组包括 6 个重复栏,每个栏包括 4 头公猪(n=24/处理)。仔猪饲喂基础日粮(CON)、基础日粮添加 20.4mg 烟酸/千克日粮(NA)或基础日粮添加 GPR109A 受体拮抗剂(MPN)。此外,还使用已建立的猪小肠上皮细胞系(IPEC-J2)来研究烟酸对大肠杆菌 K88(ETEC K88)处理后 AQPs 表达的保护作用及其潜在机制;(3)结果:与饲喂添加拮抗剂日粮的仔猪相比,饲喂添加烟酸日粮的仔猪腹泻率显著降低,结肠中 ZO-1、AQP1 和 AQP3 的 mRNA 和蛋白水平升高(p<0.05)。此外,ETEC K88 处理显著降低了 IPEC-J2 细胞的细胞活力、细胞迁移以及 AQP1、AQP3、AQP7、AQP9、AQP11 和 GPR109A 的 mRNA 和蛋白表达(p<0.05)。然而,烟酸的补充显著防止了 ETEC K88 诱导的 IPEC-J2 细胞活力、细胞迁移和 AQP mRNA 和蛋白表达水平的下降(p<0.05)。此外,siRNA GPR109A 敲低显著削弱了烟酸对 ETEC K88 诱导的细胞损伤的保护作用(p<0.05);(4)结论:烟酸补充通过 GPR109A 途径增加 AQPs 和 ZO-1 的表达,减少断奶仔猪的腹泻和肠道损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14fa/9368703/c8585fa6f699/ijms-23-08332-g007.jpg
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