高迁移率族蛋白-1在急性胰腺炎中的表达及意义

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

目的观察急性胰腺炎大鼠高迁移率族蛋白-1（HMGB1）表达水平的变化，探讨其在急性胰腺炎发病过程中的作用和意义。方法分别以2％及3．8％的牛磺胆酸钠逆行注入大鼠胰胆管，制作大鼠轻型和重症急性胰腺炎模型。将84只大鼠随机分成3组：假手术组（SO组n=28），轻型胰腺炎组（MAP组n=28），重症胰腺炎组（SAP组n=28）。对胰腺损伤进行病理评分，免疫组织化学方法观察胰腺中HMGB1的表达情况，ELISA法测定血清中HMGB1水平。结果MAP和SAP组胰腺组织HMGBl的表达在建模后12h明显升高，于24h达高峰，至48h明显下降，各时段胰腺组织HMGBl的表达与SO组比较差异具有显著统计学意义（P〈0．05）。建模后12、24、48、72hSAP组胰腺HMGBl免疫组化IOD均值明显高于MAP组（P〈0．05），胰腺HMGB1表达程度与胰腺病理损伤程度呈正相关。MAP和SAP组大鼠的血清HMGB1水平在建模后12h明显升高，于48h达高峰，至72h明显下降，各时段的血清HMGB1水平与SO组比较差异具有显著统计学意义（P〈0．05）。SAP组的血清HMGBl水平于建模后24、48、72h明显高于MAP组（P〈0．05），血清HMGB1水平与胰腺病理损伤程度呈正相关。结论HMGB1可能作为晚期炎症介质参与了胰腺炎的局部及全身炎症反应，并可作为评价胰腺炎病变和炎症反应程度的有效指标。

Objective To observe the expression of high mobility group box protein 1 （HMGB1） in rats with acute pancreatitis and explore its role and significance in acute pancreatitis. Methods Mild acute and severe acute pancreatitis rat models were induced by the biliary-pancreatic duct retroperfusion of 2 % and 3.8 % sodium taurocholate, respectively. The 84 rats were randomized into the sham-operated group, MAP group and SAP group. Pancreatic sections were stained with hematoxylin and eosin for histological analysis and scoring. The level of HMGB1 expression in pancreatic tissue was determined with immunohistochemistry and the serum HMGB1 concentration was determined by ELISA. Results Immunohistochemical assay of pancreatic HMGB1 showed that the HMGB1 expression in MAP group and SAP group increased more significantly 12 h after modeling, and reached the peak and declined remarkably 24 and 48 h after modeling, respectively. The HMGB1 expression in MAP group and SAP group was higher than that in the sham-operated one. The pancreatic HMGB1 IOD mean of SAP group increased more significantly in 12, 24, 48 and 72 hours after modeling as compared with MAP group. The HMGB1 level of pancreatic tissue was directly proportional to the degree of pancreatic pathological changes. The serum HMGB1 concentration in MAP group and SAP group increased more significantly 12 h after modeling, and reached the peak and declined greatly 48 and 72 h after modeling, respectively. The serum HMGB1 concentration of MAP group and SAP group was higher than that in sham-operated one. The serum HMGB1 concentration in SAP group increased more significantly in 24, 48 and 72 h after modeling as compared with MAP group. The serum HMGB1 level was directly proportional to the degree of pancreatic pathological changes. Conclusion HMGB1 probably participates in the pancreatitis local and systemic inflammatory reaction as a late mediator of inflammation and it could be a valid indicator to evaluate the degree of the pancreatitis and inflammatory reaction.