Abstract

In this study, we investigated the potential role of high-mobility group box 1 (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G) and somatostatin (S) in SAP rats. The rats were randomly divided into 6 groups of 20 each: sham-operated, SAP, SAP+saline, SAP+G, SAP+S and SAP+G+S. Ileum and pancreas tissues of rats in each group were evaluated histologically. HMGB1 mRNA expression was measured by reverse transcription-PCR. Levels of circulating TNF-α, IL-1, IL-6, and endotoxin were also measured. In the SAP group, interstitial congestion and edema, inflammatory cell infiltration, and interstitial hemorrhage occurred in ileum and pancreas tissues. The levels of HMGB1, TNF-α, IL-1, IL-6 and endotoxin were significantly up-regulated in the SAP group compared with those in the sham-operated group, and the 7-day survival rate was 0%. In the SAP+G and SAP+S groups, the inflammatory response of the morphological structures was alleviated, the levels of HMGB1, TNF-α, IL-1, IL-6, and endotoxin were significantly decreased compared with those in the SAP group, and the survival rate was increased. Moreover, in the SAP+G+S group, all histological scores were significantly improved and the survival rate was significantly higher compared with the SAP group. In conclusion, HMGB1 might participate in pancreas and ileum injury in SAP. Growth hormone and somatostatin might play a therapeutic role in the inflammatory response of SAP.

Highlights

  • Acute pancreatitis is a necrotic and inflammatory process that suddenly occurs in peripheral and internal regions of the pancreas [1]

  • We investigated the potential role of high-mobility group box 1 (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G) and somatostatin (S) in SAP rats

  • The levels of HMGB1, tumor necrosis factor (TNF)-a, IL-1, IL-6 and endotoxin were significantly up-regulated in the SAP group compared with those in the sham-operated group, and the 7-day survival rate was 0%

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Summary

Introduction

Acute pancreatitis is a necrotic and inflammatory process that suddenly occurs in peripheral and internal regions of the pancreas [1]. SAP is characterized by the development of a systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) as well as local pancreatic complications, and is associated with a mortality rate of 15-30%, despite continuing improvement in clinical care [3,4]. High-mobility group box 1 (HMGB1), a large group of low-molecular-weight (,30 kDa) nucleoproteins, belongs to the largest and best characterized group of nonhistone chromosomal proteins [7]. It was originally identified as a DNA-binding protein possessing potent proinflammatory properties [8].

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