Matsuzaki Y, Sugimoto H, Hamana K, Nagamine T, Matsuzaki S, Mori M
First Department of Internal Medicine, School of Medicine, Gunma University, Maebashi, Japan.
J Hepatol. 1997 Jul;27(1):193-200. doi: 10.1016/s0168-8278(97)80301-7.
BACKGROUND/AIMS: During endotoxic shock, arachidonic acid is released from the inflammatory cell membranes and is metabolized to form eicosanoids, which modify the deleterious effects of lipopolysaccharide (LPS) on liver function. However, it is not known which prostaglandins (PGs) or leukotrienes (LTs) are produced or how they affect the LPS-treated liver. As LPS treatment elevates hepatic ornithine decarboxylase (ODC) activity and affects the polyamine levels of the mouse liver, this study was carried out to examine the effects of eicosanoids and their inhibitors on the induction of ODC activity and polyamine levels in the LPS-treated mouse liver.
LPS in the presence or absence of other drugs was intraperitoneally administered to 6-week-old mice and the livers were then removed. The hepatic ODC activity, polyamine levels, and level of ODC mRNA were determined.
The levels of LPS-induced ODC activity, the putrescine (PUT) and N1-acetylspermidine (A-SPD) were reduced by the administration of PGE1. ODC activity was enhanced by the administration of corticosterone, AA-2414 (an antagonist of thromboxane (TX) A2) and TXB2, whereas the A-SPD level was reduced by corticosterone and AA-2414 treatment. The level of ODC mRNA changed in parallel with the change in ODC activity.
PGE1 may reduce the LPS-induced production of inflammation-accelerating cytokines and reduce the level of ODC activation. Corticosterone and AA-2414 treatment may attenuate the LPS-induced production of eicosanoids, and enhance the LPS-induced ODC activation. It is possible that the eicosanoids produced by LPS treatment inhibit ODC activation during endotoxic shock.
背景/目的：在内毒素休克期间，花生四烯酸从炎症细胞膜释放并代谢形成类二十烷酸，后者可改变脂多糖（LPS）对肝功能的有害影响。然而，尚不清楚会产生哪些前列腺素（PGs）或白三烯（LTs），以及它们如何影响LPS处理的肝脏。由于LPS处理会提高肝脏鸟氨酸脱羧酶（ODC）活性并影响小鼠肝脏的多胺水平，因此进行本研究以检测类二十烷酸及其抑制剂对LPS处理的小鼠肝脏中ODC活性诱导和多胺水平的影响。
将有或无其他药物存在时的LPS腹腔注射给6周龄小鼠，然后取出肝脏。测定肝脏ODC活性、多胺水平和ODC mRNA水平。
给予PGE1可降低LPS诱导的ODC活性水平、腐胺（PUT）和N1-乙酰亚精胺（A-SPD）水平。给予皮质酮、AA-2414（血栓素（TX）A2拮抗剂）和TXB2可增强ODC活性，而皮质酮和AA-2414处理可降低A-SPD水平。ODC mRNA水平的变化与ODC活性的变化平行。
PGE1可能减少LPS诱导的促炎细胞因子的产生并降低ODC激活水平。皮质酮和AA-2414处理可能减弱LPS诱导的类二十烷酸的产生，并增强LPS诱导的ODC激活。LPS处理产生的类二十烷酸可能在内毒素休克期间抑制ODC激活。
