Research Institute of General Surgery, Jinling Hospital, 305 Zhongshan East Road, Nanjing 210002, China.
Clin Nutr. 2012 Dec;31(6):951-7. doi: 10.1016/j.clnu.2012.03.003. Epub 2012 May 2.
BACKGROUND & AIMS: This study was designed to investigate whether n-3 PUFAs attenuate ischemia/reperfusion (I/R) induced intestinal barrier injury by activating I-FABP-PPARγ pathway.
24 Male Sprague-Dawley rats were assigned to 4 groups: control group, I/R group, pretreated with n-3 PUFAs for 7 days before I/R (group 3), pretreated with peroxisome proliferator-activated receptor (PPARγ) agonist 30 min before I/R (group 4). The serum and intestinal mucosa samples were collected.
I/R disrupted the structure of intestinal tight junctions (TJs) and reduced occludin expression. The intestinal fatty acid binding protein (I-FABP) was elevated in plasma while decreased in cells. PPARγ expression in nucleus of intestinal mucosa was attenuated. N-3 PUFAs attenuated the damaged TJ structure and elevated occludin, intracellular I-FABP and PPARγ expression. A PPARγ agonist had the same effect as n-3 PUFAs.
The intestinal barrier is severely damaged after I/R, which is related to the redistribution of I-FABP. Our findings firstly indicate that n-3 PUFAs protect the intestinal barrier by modifying intracellular I-FABP, activating the PPARγ pathway, and then upregulating TJ protein expression.
本研究旨在探讨 n-3 多不饱和脂肪酸(PUFAs)是否通过激活 I-FABP-PPARγ 通路来减轻缺血/再灌注(I/R)引起的肠道屏障损伤。
24 只雄性 Sprague-Dawley 大鼠被分为 4 组:对照组、I/R 组、I/R 前用 n-3 PUFAs 预处理 7 天(第 3 组)、I/R 前用过氧化物酶体增殖物激活受体(PPARγ)激动剂预处理 30 分钟(第 4 组)。收集血清和肠黏膜样本。
I/R 破坏了肠道紧密连接(TJs)的结构,降低了 occludin 的表达。肠脂肪酸结合蛋白(I-FABP)在血浆中升高,而在细胞中降低。肠黏膜细胞核中 PPARγ 的表达减弱。n-3 PUFAs 减轻了受损的 TJ 结构,并提高了 occludin、细胞内 I-FABP 和 PPARγ 的表达。PPARγ 激动剂具有与 n-3 PUFAs 相同的作用。
I/R 后肠道屏障严重受损,这与 I-FABP 的重新分布有关。我们的研究结果首次表明,n-3 PUFAs 通过修饰细胞内 I-FABP、激活 PPARγ 通路,然后上调 TJ 蛋白表达来保护肠道屏障。