Adaptive response activated by dietary cis9, trans11 conjugated linoleic acid prevents distinct signs of gliadin-induced enteropathy in mice
Adaptive response activated by dietary cis9, trans11 conjugated linoleic acid prevents distinct signs of gliadin-induced enteropathy in mice
复制标题
DOI：
10.1007/s00394-015-0893-2
复制
发表时间：
2016-03-01
影响因子：
5
通讯作者：
Rossi, Mauro
中科院分区：
文献类型：
--
作者：
Bergamo, Paolo;Palmieri, Gianna;Rossi, Mauro
共轭亚油酸(CLA)混合物(cis9，ans11，c9；Trans10，cis12，t10)对抗醇溶蛋白诱导的转基因小鼠(DQ8)的毒性作用与改善十二指肠细胞保护机制[核因子-E2相关因子-2，NRF2；酰基肽水解酶(APEH)/蛋白酶体]有关。本研究旨在探讨不同CLA异构体对醇溶蛋白和吲哚美辛(GI)联合应用所致十二指肠损伤的保护作用。在DQ8小鼠中，分别给予醇溶蛋白(20 mg kg(-1)/bw)和消炎痛(15 mg L-1)灌胃10天(GI)，建立DQ8小鼠谷蛋白介导性肠病模型。C9或T10共轭亚油酸(CLA)520 mg kg(-1)/bw/d，口服2周。采用酶学、免疫印迹、组织学评价和实时定量聚合酶链式反应等方法，评价了GI对DQ8小鼠十二指肠的促氧化和毒性作用、c9或t10-CLA的抗氧化/解毒能力以及c9预处理(c9+Gi)的保护作用。不同CLA异构体对APEH/蛋白酶体途径的影响不明显，但c9可显著改善十二指肠氧化还原状态和Nrf2激活酶的活性/mRNA水平。C9对GI介导的氧化应激标志物的聚集具有保护作用，组织学检查显示小鼠十二指肠杯状细胞数量增加，但仅诱导APEH/蛋白酶体活性的部分恢复。低剂量补充C9的激活和适应性反应阻止了DQ8小鼠明显的醇溶蛋白诱导的肠病迹象。
The beneficial effects of conjugated linoleic acid (CLA) mixture (cis9, trans11, c9; trans10, cis12, t10) against gliadin-induced toxicity in HLA-DQ8-transgenic mice (DQ8) have been associated with improved duodenal cytoprotective mechanisms [nuclear factor-E2-related factor-2, Nrf2; acylpeptide hydrolase (APEH)/proteasome]. The present study was aimed at investigating the ability of individual CLA isomers to improve the efficacy of these defensive mechanisms and to protect against duodenal injury caused by the combined administration of gliadin and indomethacin (GI).Gluten-mediated enteropathy was induced in DQ8 mice by three intra-gastric administration of gliadin (20 mg kg(-1)/bw) and indomethacin (15 mg L-1) in drinking water for 10 days (GI). C9 or t10 CLA (520 mg kg(-1)/bw/day) were orally administered for 2 weeks. Pro-oxidant and toxic effects associated with GI treatment, anti-oxidant/detoxifying ability of c9 or t10-CLA and the protective effect induced by c9 pre-treatment (c9 + GI) were evaluated in DQ8 mice duodenum by combining enzymatic, immunoblotting, histological evaluation and quantitative real-time PCR assays.GI treatment produces the time-dependent decline of the considered detoxifying mechanisms thus leading to pro-apoptotic and pro-oxidant effects. APEH/proteasome pathway was not markedly affected by individual CLA isomers, but duodenal redox status and activity/mRNA levels of Nrf2-activated enzymes were significantly improved by c9 administration. c9 pre-treatment protects against GI-mediated accumulation of oxidative stress markers, and histological examination reveals the increase of goblet cells number in mouse duodenum but induces only a partial recovery of APEH/proteasome activity.The activation of and adaptive response by low doses of c9 supplementation prevents distinct signs of gliadin-induced enteropathy in DQ8 mice.