Serizawa A, Nakamura S, Baba S, Nakano M
Second Department of Surgery, Hamamatsu University School of Medicine, Japan.
Hepatology. 1996 Jun;23(6):1656-63. doi: 10.1002/hep.510230649.
Although platelet-activating factor (PAF) is implicated as an important mediator in the pathogenesis of hepatic ischemia-reperfusion (IR) injury, the precise mechanism of its action has not been studied. We examined the hypothesis that PAF may influence neutrophils by promoting the production of tumor necrosis factor alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 (IL-8) family, and may be associated with liver and lung injury during the early phase of reperfusion after total hepatic ischemia. Rats pretreated with a specific PAF receptor antagonist exhibited suppression of the increase in plasma TNF-alpha and CINC levels, as well as the priming of peripheral neutrophils for superoxide production after reperfusion when compared with animals pretreated with physiological saline. These effects resulted in a reduction of plasma liver enzymes and of hepatic and pulmonary neutrophil sequestration, as well as an increased survival rate. There was a strong correlation between the time course of CINC release and hepatic or pulmonary neutrophil sequestration. We concluded that PAF activates neutrophils, either directly or by promoting the production of TNF-alpha and CINC, and is involved in hepatic IR injury.
尽管血小板活化因子（PAF）被认为是肝缺血再灌注（IR）损伤发病机制中的一种重要介质，但其确切作用机制尚未得到研究。我们检验了以下假说：PAF可能通过促进肿瘤坏死因子α（TNF-α）和细胞因子诱导的中性粒细胞趋化因子（CINC，白细胞介素-8（IL-8）家族的一员）的产生来影响中性粒细胞，并且可能与全肝缺血后再灌注早期的肝和肺损伤有关。与用生理盐水预处理的动物相比，用特异性PAF受体拮抗剂预处理的大鼠在再灌注后血浆TNF-α和CINC水平的升高受到抑制，外周中性粒细胞产生超氧化物的预激发也受到抑制。这些作用导致血浆肝酶水平降低、肝和肺中性粒细胞滞留减少以及存活率提高。CINC释放的时间进程与肝或肺中性粒细胞滞留之间存在很强的相关性。我们得出结论，PAF直接或通过促进TNF-α和CINC的产生来激活中性粒细胞，并参与肝IR损伤。
