糖皮质激素受体和热休克蛋白70在大鼠重症急性胰腺炎中的表达

目的 探讨糖皮质激素受体(glucocorticoid receptor,GR)和热休克蛋白70(heat shock protein70,HSP70)在大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)中的变化及意义.方法 48只健康雄性SD大鼠,随机分成SAP组、阻断GR组和正常对照组,每组16只.采用逆行胆胰管注射牛磺胆酸钠造成SAP模型,制模前15 h肌注10%Ru486(米非司酮)油剂(按5 mg/kg体质量肌肉注射)阻断GR50%.12 h后分别活杀观察胰腺、肝、肾、肺、小肠的病理改变并采用免疫印迹法测定各组织的GR,HSP70含量.结果 SAP组和阻断GR组大鼠各组织的GR水平明显低于正常对照组(P＜0.01),HSP70明显高于正常对照组(P＜0.01).阻断GR组各组织的GR和HSP70含量明显低于SAP组(P＜0.01).12 h时模型组大鼠的胰腺、肝、肾、肺、小肠已有明显的病理改变,阻断GR模型组的病理改变较SAP组明显加重.结论 在重症急性胰腺炎大鼠模型中存在GR水平的降低和HSP70水平的升高,GR不足是导致重症急性胰腺炎早期继发性肝、肾、肺、小肠损伤的重要原因,它可能通过HSP70表达下降起作用.

Expression of glucocorticoid receptor and heat shock protein 70 in severe acute pancreatitis in rats

Objective To explore the changes and significance of glucocorticoid receptor(GR) and heat shock protein 70 (HSP70) in severe acute pancreatitis(SAP) in rats. Methods The model of SAP was established with retrograde injection of sodium taurocholate into the pancreatic duct. Forty-eight rats were randomized into SAP group( n=16 ) ,blocked GR group (n=16) and control group(n=16). GR was blocked with mifepristone 15 hours before models were made. The rats were killed after 12 hours, and pancreas,liver, kidneys, lungs and small intestine were examined. The contents of GR and HSP70 in tissue were assayed with western blotting. Results In SAP group, the contents of GR in tissues were lower and the contents of HSP70 were higher than those in control group. In blocked GR group, the contents of GR and HSP70 were lower than that in SAP group. Significant pathological alterations were found in models of in pancreas,liver, kidneys, lungs and small intestine, the pathological alteration in blocked GR group were more severe than that in SAP group. Conclusion The contents of GR decrease and the contents of HSP70 increase in rats with severe acute pancreatitis, glucocorticoid receptor insufficiency can cause secondary injury of liver, kidneys, lungs and small intestines in early stage in acute severe pancreatitis. HSP70 may participate in initiating anti-injury mechanism.