van Dijk A P, McCafferty D M, Wilson J H, Zijlstra F J
Dept. of Pharmacology, Erasmus University, Rotterdam, The Netherlands.
Agents Actions. 1993;38 Spec No:C120-1. doi: 10.1007/BF01991157.
This study was performed to determine whether 15-HETE, which is the major metabolite of arachidonic acid (AA) in inflamed and normal human colonic tissue, has pro- or anti-inflammatory properties. To investigate these effects, 15-HETE (100 micrograms/kg/day) was administered rectally to mice with colitis induced by dextran sodium sulphate (DSS). Colons were removed and examined macroscopically and histologically and specimens were incubated with [14C]-AA and stimulated with A23187. Exogenous eicosanoids were separated by HPLC; the endogenously formed mediators were measured by radioimmunoassay. DSS produced a marked diffuse inflammatory response in the colon, associated with a raised inflammation score (mean 7.6 vs. < 0.5) and a significant increase in endogenously formed metabolites PGE2, LTB4 and 12-HETE. 15-HETE treatment resulted in a slight decrease in inflammation score (6.4 vs. 7.6) and a slight, but not significant, decrease in endogenous LTB4.
本研究旨在确定15-羟基二十碳四烯酸(15-HETE),即发炎和正常人类结肠组织中花生四烯酸(AA)的主要代谢产物,是否具有促炎或抗炎特性。为研究这些作用,将15-HETE(100微克/千克/天)经直肠给予葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠。切除结肠并进行大体和组织学检查,将标本与[14C]-AA一起孵育并用A23187刺激。通过高效液相色谱法分离外源性类花生酸;通过放射免疫测定法测量内源性形成的介质。DSS在结肠中产生明显的弥漫性炎症反应,伴有炎症评分升高(平均7.6对<0.5)以及内源性形成的代谢产物前列腺素E2(PGE2)、白三烯B4(LTB4)和12-羟基二十碳四烯酸(12-HETE)显著增加。15-HETE治疗导致炎症评分略有下降(6.4对7.6),内源性LTB4略有下降,但不显著。