Zhou W G, Chao W, Levine B A, Olson M S
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
Am J Pathol. 1990 Dec;137(6):1501-8.
The role of platelet-activating factor (PAF) as a mediator of pancreatic inflammation was examined in the rat pancreatic duct ligation model of obstructive pancreatitis. Pancreatic generation of PAF, as measured by bioassay (ie, platelet [3H]serotonin secretion), was determined at various times after induction of inflammation. Tissue levels of PAF in the normal pancreas averaged 600 +/- 49 pg/g, but PAF was not detectable during the initial 24 hours of pancreatitis, a time when the inflammatory reaction would be considered acute, that is, during the period of maximal serum amylase release and the development of interstitial edema. However a substantial increase in pancreatic PAF levels (12 times control levels) was observed 7 to 14 days after duct ligation during the late-phase response interval similar to the situation characteristic of chronic pancreatitis in which parenchymal atrophy, fibrosis, and pancreatic insufficiency evolve. One week after duct ligation when PAF levels peaked, an evaluation was made of the effects of PAF antagonists (BN52021 and WEB2170) on pancreatic lesions using Evan's blue extravasation, pancreatic myeloperoxidase (MPO) activity, and acid phosphatase activity in peritoneal lavage fluid. BN52021 or WEB2170 treatment was shown to reduce pancreatic damage and inflammation significantly. Long-term in vivo administration of exogenous PAF (20 micrograms/kg/hr for 7 days) exhibited a reduction of [3H]thymidine uptake into and amylase release from pancreatic acini in vitro. Our observations 1) that pancreatic PAF levels increased significantly during the chronic phase of obstructive pancreatitis induced by duct ligation; 2) that inhibition of the action of PAF, through specific receptor antagonism, caused an attenuation of pancreatic lesions; and 3) that chronic administration of PAF resulted in decreased pancreatic regeneration and exocrine function are consistent with a pivotal role for PAF as a late-phase inflammatory mediator in chronic pancreatitis in rats.
在大鼠梗阻性胰腺炎胰管结扎模型中，研究了血小板活化因子（PAF）作为胰腺炎症介质的作用。通过生物测定法（即血小板[3H]5-羟色胺分泌）测定炎症诱导后不同时间胰腺中PAF的生成量。正常胰腺组织中PAF水平平均为600±49 pg/g，但在胰腺炎发作后的最初24小时内未检测到PAF，这一时期的炎症反应被认为是急性的，即处于血清淀粉酶释放量最大和间质水肿发展的阶段。然而，在结扎导管7至14天后的晚期反应期，观察到胰腺PAF水平大幅升高（为对照水平的12倍），这一时期类似于慢性胰腺炎的特征性情况，即实质萎缩、纤维化和胰腺功能不全逐渐发展。导管结扎一周后PAF水平达到峰值，使用伊文思蓝外渗、胰腺髓过氧化物酶（MPO）活性和腹腔灌洗液中的酸性磷酸酶活性，评估了PAF拮抗剂（BN52021和WEB2170）对胰腺病变的影响。结果显示，BN52021或WEB2170治疗可显著减轻胰腺损伤和炎症。长期体内给予外源性PAF（20微克/千克/小时，持续7天）可使体外胰腺腺泡对[3H]胸腺嘧啶的摄取量以及淀粉酶释放量减少。我们的观察结果如下：1）在导管结扎诱导的梗阻性胰腺炎慢性期，胰腺PAF水平显著升高；2）通过特异性受体拮抗作用抑制PAF的作用可减轻胰腺病变；3）长期给予PAF会导致胰腺再生和外分泌功能降低。这些结果表明，PAF在大鼠慢性胰腺炎的晚期炎症介质中起关键作用。
