Li Lei, Wang Xing-Peng, Wu Kai
Department of Gastroenterology, Shanghai First People's Hospital, Institute of Pancreas Diseases, Shanghai Jiao Tong University, Shanghai, China.
Pancreas. 2007 Oct;35(3):e27-36. doi: 10.1097/mpa.0b013e3181525855.
This study aims to investigate the therapeutic effect of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OXPAPC) in rodents with acute necrotizing pancreatitis (ANP) and its mechanism.
The ANP model was induced by cerulein challenged by lipopolysaccharide in mice and taurocholic acid in Sprague-Dawley rats. Both ANP models were treated with OXPAPC. Twenty animals of each group were separated to investigate mortality. Detection included serum levels of amylase and lactate dehydrogenase, histological changes of pancreas, activity of myeloperoxidase in pancreas, mRNA expression of inflammatory factors, expression of signal transduction factor proteins, and binding activity of transcriptional factors.
After treatment with OXPAPC, survival rate was improved in the rat model. In both models, OXPAPC significantly decreased serum amylase and lactate dehydrogenase levels. Histologically, OXPAPC reduced the severity of pancreatic injury. There was a significant decline of myeloperoxidase activity. The mRNA levels of intrapancreatic inflammatory factors were depressed. Activated p38, C-jun N-terminal kinase 1, and inhibitor of kappa-B kinase beta proteins were down-regulated. Electrophoretic mobility shift assay showed that the binding activity of nuclear factor-kappaB and activator protein 1 to DNA was inhibited.
The OXPAPC decreased the severity of experimental ANP in rodents. The protective effect of OXPAPC was mediated, at least in part, through blocking the lipopolysaccharide signal pathway.
本研究旨在探讨氧化型1-棕榈酰-2-花生四烯酰-sn-甘油-3-磷酸胆碱（OXPAPC）对急性坏死性胰腺炎（ANP）啮齿动物的治疗作用及其机制。
通过脂多糖刺激的蛙皮素诱导小鼠ANP模型，以及牛磺胆酸诱导Sprague-Dawley大鼠ANP模型。两种ANP模型均用OXPAPC治疗。每组20只动物用于研究死亡率。检测指标包括血清淀粉酶和乳酸脱氢酶水平、胰腺组织学变化、胰腺髓过氧化物酶活性、炎症因子mRNA表达、信号转导因子蛋白表达以及转录因子结合活性。
用OXPAPC治疗后，大鼠模型的存活率提高。在两种模型中，OXPAPC均显著降低血清淀粉酶和乳酸脱氢酶水平。组织学上，OXPAPC减轻了胰腺损伤的严重程度。髓过氧化物酶活性显著下降。胰腺内炎症因子的mRNA水平降低。活化的p38、C- Jun氨基末端激酶1和κB激酶β抑制蛋白下调。电泳迁移率变动分析表明，核因子-κB和活化蛋白1与DNA的结合活性受到抑制。
OXPAPC减轻了啮齿动物实验性ANP的严重程度。OXPAPC的保护作用至少部分是通过阻断脂多糖信号通路介导的。
