Expression and significance of high mobility group box 1 in rats with acute pancreatitis

Abstract

Objective To research the role of high mobility group box 1 (HMGB1) in systemic inflammatory response in rats with acute pancreatitis (AP).Methods The 136 Spragye-Dawley rats were randomly divided into three groups:group A (n =8),group B (n =64) and group C (n =64).AP models were induced by retrograde injection of sodium taucrocholate into the biliopancreatic duct:with 2％ sodium taucrocholate to induce mild AP,and 5％ to induce severe AP in group B and group C respectively.Group C received ethyl pyruvate (EP) solution (28 mmol/L,40 mg/kg·6 h) by tail vein beginning at 2nd h after induction of AP,while group B received the same amount of ringer lactate solution balance as a placebo.The samples of the blood and pancreas were collected directly in group A,and after 6,12,24 and 48 h,the blood and pancreas were collected in groups B and C.Reverse transcription-polymerase chain reaction (RT-PCR) Western blotting were ued to detect mRNA and protein expression of HMGB1 respectively.A point scoring system histologic features were respectively used to evaluate the severity of pancreatitis,and correlation between HMGB1 mRNA expression and pancreatic histopathological score was analyzed.Results The expression levels of HMGB1 mRNA and the pancreas pathological scores in group A were 1.01 ±0.18 and 0.70 ±0.23 separately.The HMGB1 mRNA expression in the pancreatic tissue of group B at 6th,12th,24th and 48th h was separately 1.18 ±0.31,18.23 ± 1.36,201.14 ± 12.01 and 190.66 ± 9.77,with histopathological scores of the pancreas being 9.01 ± 1.94,9.97 ± 1.81,11.45 ±1.43 and 13.17 ± 1.37.The HMGB1 mRNA expression in the pancreatic tissue of group C at at 6th,12th,24th and 48th h was separately 1.11 ±0.27,12.60 ± 1.20,45.44 ±4.45,and 41.41 ±4.11,and histopathological scores of the pancreas were 8.97 ± 1.87,9.92 ± 1.88,9.34 ± 1.63 and 10.26 ± 1.22 separately.The correlation coefficient of HMGB1 mRNA in pancreatic tissues and pancreatic histopathological scores in groups A and B was r =0.847 (P ＜ 0.01).Conclusion The expression of HMGB1 was increased at 12th h,reached the peak at 24th h and stayed at a high level at 48th h.The increased HMGB1 was positively correlated wtih the severity of AP,suggesting its importanthy role in the systemic inflammatory response of AP.Treatment with EP has a therapeutic effect on AP by inhibitting HMGB1 expression,and reducing pancreatic injury. Key words: Acute pancreatitis ; High mobility group box 1 ; Ethyl pyruvate