Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food Science and Pharmaceutics, Zhejiang Ocean University, Zhoushan 316022, China.
Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou 313000, China.
Int J Mol Sci. 2019 Nov 15;20(22):5727. doi: 10.3390/ijms20225727.
Low molecular seleno-aminopolysaccharide (LSA) was synthesized with sodium selenite and low molecular aminopolysaccharide (LA), which is an organic selenium compound. This study is aimed to investigate the protective effect of LSA on the intestinal mucosal barrier in weaning stress rats by detecting the intestinal tissue morphology and function, mucosal thickness and permeability, the structure of MUC2, antioxidant index, the expression level of intracellular transcription factor NF-E2-related factor 2 (Nrf2), and its related factors. The results showed that LSA significantly increased the height of intestinal villi ( < 0.05) and increased the thickness of intestinal mucosa and the number of goblet cells, which indicated that LSA has a protective effect on the intestinal mucosal barrier that is damaged by weaning. Moreover, LSA significantly reduced the level of DAO, D-LA, and LPS compared with the weaning group ( < 0.05), which indicated that LSA reduced the intestinal damage and permeability of weaning rats. In addition, LSA could increase the number and length of glycans chains and the abundance of acid glycans structures in the MUC2 structure, which indicated that LSA alleviated the changes of intestinal mucus protein structure. LSA significantly increased the levels of GSH-Px, SOD, LDH, and CAT, while it decreased the level of MDA in serum and intestinal tissue, which suggested that LSA significantly enhanced the antioxidant capacity and reduced oxidative stress of weaning rats. RT-PCR results showed that LSA significantly increased the expression level of antioxidant genes (GSH-Px, SOD, Nrf2, HO-1), glycosyltransferase genes (GalNT1, GalNT3, GalNT7) and mucin gene (MUC2) in intestinal mucosa ( < 0.05). The results of western blot showed that the LSA activated the Nrf2 signaling pathway by down-regulating the expression of Keap1and up-regulating the expression of Nrf2, and protected the intestinal mucosa from oxidative stress. Overall, LSA could play a protective role in intestinal mucosal barrier of weaning rats by activating the Nrf2 pathway and alleviating the alnormal change of mucin MUC2.
低分子硒-氨基多糖（LSA）是由亚硒酸钠和低分子氨基多糖（LA）合成的一种有机硒化合物。本研究旨在通过检测肠道组织形态和功能、黏膜厚度和通透性、MUC2 结构、抗氧化指标、细胞内转录因子 NF-E2 相关因子 2（Nrf2）及其相关因子的表达水平，探讨 LSA 对断奶应激大鼠肠道黏膜屏障的保护作用。结果表明，LSA 显著增加了肠绒毛高度（<0.05），增加了肠黏膜厚度和杯状细胞数量，表明 LSA 对断奶损伤的肠道黏膜屏障具有保护作用。此外，与断奶组相比，LSA 显著降低了DAO、D-LA 和 LPS 的水平（<0.05），表明 LSA 减轻了断奶大鼠的肠道损伤和通透性。此外，LSA 可以增加 MUC2 结构中糖链的数量和长度以及酸性糖结构的丰度，表明 LSA 缓解了肠道黏液蛋白结构的变化。LSA 显著提高了血清和肠道组织中 GSH-Px、SOD、LDH 和 CAT 的水平，同时降低了 MDA 的水平，表明 LSA 显著增强了断奶大鼠的抗氧化能力，减轻了氧化应激。RT-PCR 结果表明，LSA 显著增加了肠道黏膜中抗氧化基因（GSH-Px、SOD、Nrf2、HO-1）、糖基转移酶基因（GalNT1、GalNT3、GalNT7）和黏蛋白基因（MUC2）的表达水平（<0.05）。Western blot 结果表明，LSA 通过下调 Keap1 表达和上调 Nrf2 表达激活了 Nrf2 信号通路，从而保护肠道黏膜免受氧化应激。总之，LSA 通过激活 Nrf2 通路和缓解黏蛋白 MUC2 的异常变化，在断奶大鼠肠道黏膜屏障中发挥保护作用。
