摘要
目的探讨磷脂酰肌醇3激酶/蛋白激酶B(PI3K/PKB)信号转导通路对重症急性胰腺炎胰腺损伤的作用。方法健康成年雄性SD大鼠30只,随机分为对照组、SAP组(S组)和SAP+wort-mannin(S+W)组,每组10只。胆胰管内逆行注射法制作SAP模型。制模6h后取胰腺组织,检测各组含水量、MPO水平及病理改变;采用酶联免疫吸附法(ELISA)及RT-PCR技术检测胰腺组织TNF-α和IL-1β的蛋白及mRNA的变化、蛋白印迹(WesternBlot)法检测p-PKB的活性变化。结果制模6h后S组和S+W组较对照组胰腺组织含水量增加(P<0.01),MPO水平明显升高(P<0.01);病理学发现胰腺明显出血、坏死和炎性细胞浸润;胰腺组织TNF-α和IL-1β的蛋白及mRNA水平明显增加(P<0.01),p-PKB水平明显升高(P<0.01)。S+W组较S组胰腺组织水肿及病理改变减轻(P<0.01)、MPO水平降低(P<0.01),同时TNF-α和IL-1β的蛋白含量及mRNA表达减少(P<0.01),p-PKB水平降低(P<0.01)。结论PI3K/PKB信号传导通路被激活是重症急性胰腺炎胰腺损伤的重要发病机制之一。
Objective To investigate the role of PI3 K/PKB signal transduction pathway in the injury of pancreas during severe acute pancreatitis. Methods Thirty adult healthy SD rats were randomized into three groups ： control group, SAP group （ group S ） and SAP ＋ wortmannin group （ group S ＋ W ） . SAP models were established by retrograde injection of 5 % sodium taurocholate into pancreatic duct. Rats from each group were killed at 6 h after SAP models had been established. Pancreas water content, MPO and pancreatic histology were measured, meanwhile, protein and mRNA levels of TNF-α and IL-1β in pancreas were examined by ELISA and RT-PCR respectively. Levels of phosphorylated PKB （ p-PKB ） and total PKB were examined by western blotting. Results Pancreatitis （ group S and group S ＋ W ） resulted in elevated pancreas water content, increased MPO, and worsened histologic condition （ P 〈 0.01 ）. Protein and mRNA levels of TNF-α and IL-1β from SAP rats were much higher than those in shams （P 〈 0.01 ）. p-PKB activity presented similar tendency （ P 〈 0.01 ）. In S ＋ W group pancreas water content markedly decreased, MPO reduced, and degree of pancreatic injury reduced （ P 〈 0.01 ）. At the same time, wortmannin inhibited the activation of p- PKB and decreased protein and mRNA levels of TNF-α and IL-1β （ P 〈 0.01 ）.Conclusions The activation of PI3 K/PKB is one important aspect of the signaling event that contributes to the injury of pancreas during severe acute pancreatitis.
出处
《中国普通外科杂志》
CAS
CSCD
2007年第10期968-971,共4页
China Journal of General Surgery
关键词
胰腺炎
急性坏死性
磷脂酰肌醇3激酶
蛋白激酶B
信号转导
Pancreatitis, Acute Necrotizing
Phosphatidylinositol 3 -Kinase
Protein Kinase B
Signal Transduction
