Published online Mar 28, 2017. doi: 10.3748/wjg.v23.i12.2175
Peer-review started: December 11, 2016
First decision: January 10, 2017
Revised: January 18, 2017
Accepted: February 16, 2017
Article in press: February 17, 2017
Published online: March 28, 2017
Processing time: 108 Days and 23.1 Hours
To examine the effects of Acanthopanax senticosus polysaccharides (ASPS) on intestinal tight junction (TJ) disruption and nuclear factor-kappa B (NF-κB)/myosin light chain kinase (MLCK) activation in endotoxemia.
BALB/C mice (6-8-weeks-old) received continuous intragastric gavage of ASPS for 7 d before injection of lipopolysaccharide (LPS), or received ASPS once after LPS injection. Blood and intestinal mucosal samples were collected 6 h after LPS challenge. Clinical symptoms, histological injury, intestinal permeability, TJ ultrastructure, and TJ protein expression were determined.
Compared with mice in the LPS group, pretreatment with ASPS improved clinical and histological scores by 390.9% (P < 0.05) and 57.89% (P < 0.05), respectively, and gut permeability change in endotoxemic mice was shown by a 61.93% reduction in reduced leakage of fluorescein isothiocyanate-dextran 6 h after LPS injection (P < 0.05). ASPS pretreatment also prevented LPS-induced TJ ultrastructure breakdown supported by increased electron dense materials between adjoining cells, sustained redistribution and expression of occludin (0.597 ± 0.027 vs 0.103 ± 0.009, P < 0.05) and zonula occludens-1 (0.507 ± 0.032 vs 0.125 ± 0.019, P < 0.05), and suppressed activation of the NF-κB/MLCK pathway indicated by reduced expression of NF-κB, phospho-inhibitor kappa B-alpha, MLCK and phospho-myosin light-chain-2 by 16.06% (P < 0.05), 54.31% (P < 0.05), 66.10% (P < 0.05) and 64.82% (P < 0.05), respectively.
ASPS pretreatment may be associated with inhibition of the NF-κB/MLCK pathway and concomitant amelioration of LPS-induced TJ dysfunction of intestinal epithelium in endotoxemia.
Core tip:Acanthopanax senticosus polysaccharides (ASPS) effectively protect against gastric tight junction (TJ) injury in sepsis. ASPS pretreatment significantly improved intestinal histological appearance and gut permeability, increased electron dense between adjoining cells, sustained the expression and redistribution of occludin and zonula occludens-1, suppressed the expression of nuclear factor-kappa B p65 (NF-κBp65) and phospho-inhibitor kappa B-alpha and myosin light chain kinase (MLCK), as well as phospho-myosin light-chain-2 in endotoxemia. These findings suggest that ASPS pretreatment may be associated with inhibition of the NF-κB/MLCK pathway and concomitant amelioration of gastric TJ dysfunction in the mouse model of endotoxemia.