title: Effects of gut barrier dysfunction and NF-kappaB activation on aggravating mechanism of severe acute pancreatitis.
abstract: OBJECTIVE
  To study the effects of gut-derived endotoxin translocation and NF-kappaB activation on the aggravating mechanism of severe acute pancreatitis (SAP) and of treatment with pyrrolidine dithiocarbamate (PDTC) on rats with SAP.
  
  
  METHODS
  SD rats were randomly divided into sham operation group (SO), SAP group, SAP + lipopolysaccharide(LPS) group, pyrrolidine dithiocarbamate (PDTC) treatment group and LPS group. Biochemical parameters and cytokines were examined in the serum. Multiple organs pathological slices were examined. Expression of NF-kappaB mRNA in the liver tissue was detected by RT-PCR. Activation of NF-kappaB by the method of streptomycin avidin-peroxidase (SP) and expression of NF-kappaB p65 protein and its binding activity were analyzed by Western blot and electrophoretic mobidity shift assay (EMSA).
  
  
  RESULTS
  Compared with sham operation group, the concentration of TNF-alpha, alanine aminotransferase (ALT), and diamine oxidase (DAO) in serum significantly increased in SAP + LPS group (P < 0.05). Pathological changes were markedly observed in tissues and the expression of NF-kappaB mRNA in the liver significantly increased (P < 0.05) also, the activation of NF-kappaB and binding activity of NF-kappaB p65 protein in the liver markedly increased (P < 0.01) in SAP + LPS group. Treatment with PDTC markedly reduced concentration of ALT, DAO and TNF-alpha, and the expression of NF-kappaB, and the pathologic scores, as well as significantly decreased the expression of NF-kappaB p65 protein.
  
  
  CONCLUSIONS
  The activation and overexpression of NF-kappaB may participate in the aggravating mechanism of SAP. Treatment with PDTC has a protective effect on multiple organs damage in SAP.
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yi Lin
authors.initials: YL
authors.lastname: Wang
authors.forename: Yun Jiang
authors.initials: YJ
authors.lastname: Zheng
authors.forename: Zi Ping
authors.initials: ZP
authors.lastname: Zhang
authors.forename: Jing Ying
authors.initials: JY
authors.lastname: Su
authors.forename: Ruo Qing
authors.initials: RQ
authors.lastname: Lei
authors.forename: Yao Qing
authors.initials: YQ
authors.lastname: Tang
authors.forename: Sheng Dao
authors.initials: SD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D018988:Bacterial Translocation; D044682:Colon, Ascending / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D011759:Pyrrolidines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C020972:pyrrolidine dithiocarbamic acid