Role of endogenous platelet-activating factor (PAF) in stress-induced hemorrhagic pancreatitis in rats

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Recently, it has been reported that the exogenous platelet-activating factor(PAF) could induce acute pancreatitis in rabbits(l). In this study, to investigate the role of endogenous PAF in acute pancreatitis, the effect of the PAF-antagonist(CV6209, Takeda Chemical Industries Ltd, Osaka, Japan) was evaluated in stress-induced hemorrhagic pancreatitis in male SpragueDawley rats. The new model for acute pancreatitis was induced by an intraperitoneal injection of 40 ~g/kg BW of cerulein twice under waterimmersion stress at 23~ for 5 hours(2). Five hours after the treatment, the pancreas wet weight and serum amylase levels in stress-induced hemorrhagic pancreatitis were 3.95 + 0.i0 g and 48,194 + 8,001 Somogyi U/dl~mean + SEM). By one intravenous injection of lOmgTkg.BW of VC6029, 5 mins before the treatment of stress and cerulein injections, those were significantly suppressed (2.79 + 0.27 g and 28,420 + 3,683 SU/dl, respectively) but not reduced more than those of cerulein injections alone(Fig). Maeroscopically, the PAFantagonist prevented bleeding in pancreatic tissue slightly but not completely. The significant preventive effect of the PAF-antagonist suggests that endogenous PAF derived from endothelial cells, monoeytesmacrophages, polymorphonuclear neutrophils and platelets, may be one of exacerbating factors in the development of pancreatitis.

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