Effects of gut barrier dysfunction and NF-kappaB activation on aggravating mechanism of severe acute pancreatitis.
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.
Wang
Yi Lin
YL
Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Zheng
Yun Jiang
YJ
Zhang
Zi Ping
ZP
Su
Jing Ying
JY
Lei
Ruo Qing
RQ
Tang
Yao Qing
YQ
Zhang
Sheng Dao
SD
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
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