丙酮酸乙酯对重症急性胰腺炎大鼠肠黏膜HMGB1表达的影响

The effects of ethyl pyruvate on high mobility group box-1 protein expression in murine severe acute pancreatitis

目的探讨丙酮酸乙酯(EP)对大鼠重症急性胰腺炎(SAP)肠组织中高迁移率族蛋白B1(HMGB1)表达的影响,以期为SAP的治疗提供思路。方法雄性Wistar大鼠90只随机分为3组:A组为SAP组;B组为SAP+EP处理组(EP组);C组假手术对照组(对照组)。3组动物于术后3,6,12,24,48h取材。测定血淀粉酶(AMY)、D-乳酸、肠组织丙二醛(MDA)含量。通过光学显微镜观察肠组织病理变化及免疫组织化学法观察HMGB1在肠组织中的表达。Western-blot法进行HMGB1检测。结果A,B组AMY和D-乳酸水平明显升高,但B组较A组显著降低(P<0.05)。A组肠组织中MDA明显高于C组(P<0.01),B组肠组织中MDA升高幅度较A组小(P<0.05)。B组较A组肠组织病理损伤明显减轻。A组6h时肠组织HMGB1表达水平显著高于C组,于24h达峰值,且持续至48h(P<0.01)。B组肠组织HMGB1表达水平均明显低于A组(P<0.05)。结论SAP时,HMGB1可介导肠黏膜通透性增加。EP能显著抑制HMGB1的表达,改善肠黏膜屏障功能,对SAP肠黏膜损伤有明显的保护作用。

Objective To explore the effects of ethyl pyruvate （ EP ） on high mobility group box-1 protein （HMGB 1 ） expression in severe acute pancreatitis （SAP） rats. Methods Ninety male wistar rats were divided randomly into three groups ： Group A （ SAP group ） ; group B （ SAP rats received ethyl pyruvate therapy ） ; group C （control group ）. Specimens from rats in the three groups were taken at 3, 6, 12, 24 and 48 h after operation respectively. The concentration of plasma amylase and D-lactate the activity of malonyl dialdehyde （ MAD ） in the intestinal tissue were determined. The changes of morphological damage of intestinal tissue was observed by microscopy. The expression of HMGB 1 in intestinal mucosa was observed by SP immunohistochemistry and the activity of HMGB1 was determined by western blot. Results Compared with group A, levels of plasma amylase, and D-lactate in group B decreased markedly （ P 〈 0. 05 ）. Compared with group C, MDA in group A increased significantly （ P 〈 0.01 ）. Compared with group A, the pathological lesion of intestinal mucosa was improved and the expression of HMGB1 was obviously down regulated in group B （ P 〈 0.05 ）. The expression of HMGB 1 in bowel tissues in group A was increased significantly at 6h and maintained to 24h after SAP model was induced; whereas in group C, HMGB 1 expression was significantly lower than that in group A at each time point （ P 〈 O. 05 ）. Conehmions HMGB1 can mediate an increase in penetrability of intestinal mucosal barrier in SAP. EP can down-regulate HMGB 1 expression in intestinal tissues of SAP rats, improve the function of intestinal mucosal barrier, and protect intestine from injury induced by SAP.