Variation of eicosanoid production by activation of Kupffer cells.

由于佛波酯模拟内毒素的作用，我们研究了佛波酯(PMA)在大鼠肝脏灌流后对酵母多糖颗粒代谢的影响。PMA可促进酵母菌多糖颗粒和花生四烯酸诱导TX B_2和PGD_2的产生。本文观察了在硫代乙酰胺诱导的雌性SD大鼠实验性肝硬变过程中，肝巨噬细胞的反应和灌流肝脏中血小板活化因子的作用。在给予硫代乙酰胺(300 mg/L饮用水)的四周内，肝巨噬细胞数量增加和细胞体积增大先于肝硬变的改变。硫代乙酰胺处理组大鼠灌流液中由血小板活化因子诱导的PGD_2和TxB_3含量分别是对照组的7倍和5倍。酵母多糖具有模拟血小板活化因子的作用。这些结果与肝巨噬细胞和血小板活化因子在硫代乙酰胺诱导的发展性肝硬变中起重要作用的假说相一致。

Since phorbol ester mimics the actions of LPS,we investigated the metabolic alternation by zymosan-pellet after infusion of phorbol 12-myristate 13-acetate (PMA) in the perfused rat livers. PMA-infusion enhanced the production of Tx B_2 and PGD_2 by zymosan-pellet and arachidonic acid.The response of hepatic macrophages and the effects of platelet-activating factor in perfused liver were studied during production of experimental liver cirrhosis induced by thioacetamide in female Sprague-Dawley rats. Within four weeks of thioacetamide administration (300mg/L drinking water) , an increase in hepatic macrophage population and enlargement in cell size preceded the alterations characteristic of cirrhosis. The amount of PGD_2 and TxB_3 in perfusate induced by platelet-activating factor were seven-and five-fold greater, respectively, in thioacetamide-treated than in control rats. Zymosan mimicked the effects of platelet-activating factor. These results are consisted with the hypothesis that hepatic macrophages and platelet-activating factor play important roles in the development cirrhosis induced by thioacetamide.