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 (p < 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 (p < 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 (p < 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.

Low molecular weight seleno-aminopolysaccharide (LSA) is an organic selenium compound comprising selenium and low molecular weight aminopolysaccharide (LA), a low molecular weight natural linear polysaccharide derived from chitosan. LSA has been found to exert strong pharmacological activity. In this study, we aimed to investigate the protective effect of LSA on intestinal mucosal oxidative stress in a weaning piglet model by detecting the growth performance, intestinal mucosal structure, antioxidant indices, and expression level of intracellular transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and its related factors. Our results indicated that LSA significantly increased the average daily gain and feed/gain (p < 0.05), suggesting that LSA can effectively promote the growth of weaning piglets. The results of scanning electron microscope (SEM) microscopy showed that LSA effectively reduced intestinal damage, indicating that LSA improved the intestinal stress response and protected the intestinal structure integrity. In addition, diamine oxidase (DAO) and d-lactic acid (d-LA) levels remarkably decreased in LSA group compared with control group (p < 0.05), suggesting that LSA alleviated the damage and permeability of weaning piglets. LSA significantly increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) levels, but decreased malondialdehyde (MDA) level, indicating that LSA significantly enhanced the antioxidant capacity and reduced oxidative stress in weaning piglets. RT-PCR results showed that LSA significantly increased GSH-Px1, GSH-Px2, SOD-1, SOD-2, CAT, Nrf2, HO-1, and NQO1 gene expression (p < 0.05). Western blot analysis revealed that LSA activated the Nrf2 signaling pathway by downregulating the expression of Keap1 and upregulating the expression of Nrf2 to protect intestinal mucosa against oxidative stress. Collectively, LSA reduced intestinal mucosal damage induced by oxidative stress via Nrf2-Keap1 pathway in weaning stress of infants.