Otomo Y, Kanda Y, Yoshino Y, Otsuka T
Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan.
Nihon Geka Gakkai Zasshi. 1993 Mar;94(3):234-41.
In order to verify whether rat hepatocytes are capable of producing leukotrienes, Percoll density gradient centrifugation to fractionize rat hepatocytes and a radioimmunoassay of leukotrienes in the reacting solution have been performed. Also, investigated was effect of retinol (Vitamin A) on inducing the production of leukotrienes in rat Kupffer cells and hepatocytes. Incubation with endotoxin (10 micrograms/ml) for 30-60 minutes induced the production of leukotrienes in rat Kupffer cells but did not induce any such production in rat hepatocytes. On the other hand, arachidonic acid (2-20 microM) or linoleic acid (10-50 microns) did induce hepatocytes to produce leukotrienes in a dose-dependent manner. Fifteen minutes of pre-incubation with 10(-8) M of retinol inhibited an endotoxic induction of leukotrienes production in rat Kupffer cells, whereas it did not inhibit an arachidonic acid induction in rat hepatocytes. Based on these results, we have concluded that a hepatic tissue injury during sepsis is probably mediated by leukotrienes produced by the Kupffer cells and its inhibition is the mechanism of tissue protective effect of retinol. However, in further severe state even the hepatocytes may produce leukotrienes and as a consequence, a widespread destruction of hepatic tissue will occur.
为了验证大鼠肝细胞是否能够产生白三烯，已进行了用Percoll密度梯度离心法分离大鼠肝细胞以及对反应溶液中的白三烯进行放射免疫测定的实验。此外，还研究了视黄醇（维生素A）对诱导大鼠库普弗细胞和肝细胞产生白三烯的影响。用内毒素（10微克/毫升）孵育30 - 60分钟可诱导大鼠库普弗细胞产生白三烯，但在大鼠肝细胞中未诱导出此类产物。另一方面，花生四烯酸（2 - 20微摩尔）或亚油酸（10 - 50微米）确实以剂量依赖的方式诱导肝细胞产生白三烯。用10⁻⁸M视黄醇预孵育15分钟可抑制内毒素诱导的大鼠库普弗细胞产生白三烯，而它并不抑制花生四烯酸诱导的大鼠肝细胞产生白三烯。基于这些结果，我们得出结论，败血症期间的肝组织损伤可能是由库普弗细胞产生的白三烯介导的，其抑制作用是视黄醇组织保护作用的机制。然而，在更严重的状态下，即使肝细胞也可能产生白三烯，结果将发生肝组织的广泛破坏。
