Role of high-mobility group box 1 protein in the pathogenesis of intestinal barrier injury in rats with severe acute pancreatitis.
OBJECTIVE
To investigate the role of high-mobility group box 1 (HMGB1) in the development of intestinal barrier injury of severe acute pancreatitis (SAP) and to examine the effect of ethyl pyruvate (EP) on intestinal inflammation in rats with SAP.


METHODS
Rats were randomly divided into the following experimental groups: control, SAP, and EP treated. Then, the distal ileum was harvested for morphological studies, streptavidin-peroxidase immunohistochemistry examination, and Western blot analysis. The concentrations of plasma amylase, endotoxin, and diamine oxidase (DAO) and the activity of myeloperoxidase (MPO) in the intestine were determined.


RESULTS
We found that the expression of HMGB1 was up-regulated in the ileal mucosa within 6 hours and then remained elevated for more than 48 hours after SAP. Meanwhile, the levels of plasma amylase, endotoxin, and DAO and the activity of MPO in the intestinal mucosa were rapidly increased after SAP. Whereas treatment with EP significantly decreased the expression of intestinal HMGB1, the levels of plasma amylase, endotoxin, and DAO ameliorated the activity of MPO in the intestine in SAP rats.


CONCLUSIONS
Our results demonstrate that HMGB1 participates in intestinal barrier injury in SAP and EP might play a therapeutic role in intestinal inflammation in this SAP model.
Luan
Zheng-Gang
ZG
Department of Intensive Care Unit, The First Affiliated Hospital of China Medical University, Shenyang, China.
Zhang
Hao
H
Ma
Xiao-Chun
XC
Zhang
Cheng
C
Guo
Ren-Xuan
RX
D000208:Acute Disease; D006631:Amine Oxidase (Copper-Containing) / Q000097:blood; D000681:Amylases / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D018988:Bacterial Translocation; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood; D024243:HMGB1 Protein / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013656:Taurocholic Acid; D013997:Time Factors; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D004731:Endotoxins; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D011773:Pyruvates; C046522:ethyl pyruvate; D013656:Taurocholic Acid; D009195:Peroxidase; D006631:Amine Oxidase (Copper-Containing); D000681:Amylases