The effects of high mobility group box-1 protein on the expression of intestinal epithelial tight junction protein occludin in murine severe acute pancreatitis

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LUAN Zheng-gang(Department of Intensive Care Unit and Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China)
GUO Ren-xuan()
Journal Title:
Chinese Journal of Emergency Medicine
Volume 21, Issue 10, 2012
Key Word:
Pancreatitis; Intestinal mucosal barrier; High mobility group box-1 protein; Tight junction

Abstract: Objective To observe the effect of high mobility group box-1 protein (HMGB1) on the expression of intestinal epithelial tight junction protein occludin in murine severe acute pancreatitis (SAP).Methods Rat SAP model was estabilished by retrograde injection of 5 % sodium taurocholate into choledochopancreatic duct.Healthy wistar rats were divided randomly (random number) into three groups:control group,SAP group,pyrrolidine dithiocarbamate (PDTC) therapy group.Levels of plasm amylase,lipopolysaccharide (LPS) and D-lactate were determined.The changes of morphological damage of pancreasand intestinal tissues were observed by microscopy.The distribution and expression of occludin protein were observed by SP immunohistochemistry. The mRNA expression of HMGB1 in the intestinal mucosa was detected by reverse-transcription polymerase chain reaction (RT-PCR).The expressions of HMGB1 and occludin were determined by western blotting. One-way analysis of variance was performed with SPSS Windows 13.0 statistical analysis software,and a difference was accepted as significant if P < 0.05.Results In comparison with the other two groups,levels of plasma LPS and D-lactate in SAP group increased markedly at 24 h after operation,which indicated that the penetrability of intestinal mucosal barrier increased (P < 0.05 ). The expression of HMGB1 in the intestinal mucosa of SAP group increased significantly compared with control group (P < 0.05).Whereas,the expression of occludin was significantly lower than control group (P <0.05).Compared with SAP group,the expression of HMGB1 was lower and the expression of occludin was higher in PDTC group ( P < 0.05).Conclusions The over-expression of HMGB1 could down regulate the expression of occludin in intestinal tissues of SAP rats,and thus mediate an increase in penetrability of intestinal mucosal barrier.As PDTC inhibited the expression of HMGB1,the expression of occludin protein was up-regulated and the function of intestinal mucosal barrier was improved.

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