title: Acanthopanax senticosuspolysaccharides-induced intestinal tight junction injury alleviationviainhibition of NF-κB/MLCK pathway in a mouse endotoxemia model.
abstract: OBJECTIVE
  To examine the effects ofAcanthopanax senticosuspolysaccharides (ASPS) on intestinal tight junction (TJ) disruption and nuclear factor-kappa B (NF-κB)/myosin light chain kinase (MLCK) activation in endotoxemia.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 ± 0.027vs0.103 ± 0.009,P< 0.05) and zonula occludens-1 (0.507 ± 0.032vs0.125 ± 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Han
authors.affiliation: Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Li
authors.affiliation: Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Bai
authors.affiliation: Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
authors.forename: Guo-Shun
authors.initials: GS
authors.lastname: Shen
authors.affiliation: Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
authors.forename: Jia-Nan
authors.initials: JN
authors.lastname: Liu
authors.affiliation: Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D028001:Eleutherococcus / Q000737:chemistry*; D019446:Endotoxemia / Q000188:drug therapy*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010539:Permeability; D011134:Polysaccharides / Q000737:chemistry*; D015398:Signal Transduction; D019108:Tight Junctions / Q000737:chemistry*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D011134:Polysaccharides; D009219:Myosin-Light-Chain Kinase
keywords: Acanthopanax senticosus polysaccharide; Intestinal permeability; Myosin light chain kinase; Nuclear factor-kappa B; Tight junction