title: [Myosin light chain kinase involved in change of intestinal mucosal barrier function in nonalcoholic steatohepatitis mice model].
abstract: OBJECTIVE
  To investigate the role of myosin light chain kinase (MLCK) in intestinal barrier function in a mouse model with nonalcoholic steatohepatitis (NASH).
  
  
  METHODS
  The C57BL/6 mice were randomly divided into five groups including control group, nonalcoholic fatty liver (NAFL) group, NAFL administrated with MLCK inhibitor ML-7 group, nonalcoholic steatohepatitis (NASH) group, NASH administrated with ML-7 group. Plasma ALT and AST were tested. The degree of liver steatosis was assessed by hematoxylin-eosin staining on liver tissue sections.Intestinal mucosal tight junction was observed by electron microscope. The expression of MLCK on intestinal mucosa was detected by immunohistochemistry staining. The level of lipopolysaccharide (LPS) in portal vein was determined by enzyme linked immune sorbent assay (ELISA). The protein and mRNA expression of inflammatory cytokines in liver tissue were tested using ELISA and real-time PCR.
  
  
  RESULTS
  MLCK expression in intestinal mucosa was increased in NASH group compared with control group (P<0.01). The tight junctions of intestinal barrier were disrupted in NASH group and intercellular space was larger than control group [(26.60 ± 1.20) nm vs (14.90 ± 0.33) nm, P<0.05], which were improved after ML-7 administration [(14.9 0 ± 0.67) nm]. The LPS in portal vein was higher in NASH group than control group [(7.260 ± 3.184) U/L vs (2.962 ± 0.845) U/L, P<0.05], suggesting that the permeability of intestinal barrier was impaired, however the level of LPS was reduced by ML-7 [(3.772 ± 1.033) U/L, P<0.05]. ALT and AST in plasma, TNFα and IL-6 in liver tissue, the mRNA levels of TNFα and NF-κB in liver tissue were all elevated in NASH group compared with control group (all P<0.05), which were reduced by MLCK inhibitor ML-7.
  
  
  CONCLUSIONS
  Epithelia MLCK probably plays a role in intestinal barrier impairment, which is critical to the pathogenesis of NASH.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yujing
authors.initials: Y
authors.lastname: Chi
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Xiuying
authors.initials: X
authors.lastname: Pan
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiangjun
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China; Email: liuyulan@pkuph.edu.cn.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001381:Azepines / Q000378:metabolism*; D004195:Disease Models, Animal; D005234:Fatty Liver; D015850:Interleukin-6; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines; D051379:Mice; D008810:Mice, Inbred C57BL; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D009281:Naphthalenes / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha
chemical_list: D001381:Azepines; D015850:Interleukin-6; D009281:Naphthalenes; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C070571:ML 7; D009219:Myosin-Light-Chain Kinase