Fujita T, Nakajima T, Matsuma T, Nishida H, Sakuma S, Fujimoto Y
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, Japan.
Res Commun Chem Pathol Pharmacol. 1994 Jan;83(1):51-60.
The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE) on the synthesis of prostaglandins (PGs) was examined in rabbit kidney medulla microsomes. Medulla microsomes were incubated with arachidonic acid in 0.1 M-Tris/HCl buffer (pH 8.0) containing reduced glutathione and hydroquinone and the PGE2, PGF2a and PGD2 formed were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. Under our incubation conditions rabbit kidney medulla was found to produce mainly PGE2. The addition of 13-HPODE inhibited the production of all three PGs to a similar extent. 13-Hydroxyoctadecadienoic acid did not suppress the formation of PGs, indicating the requirement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on PG formation. Experiments utilizing the native fatty acid linoleic acid and tert-butyl hydroperoxide suggested the importance of the fatty acid-derived hydroperoxide in PG synthesis by kidney medulla. We conclude that 13-HPODE is an inhibitor of renomedullary cyclooxygenase and may have functional effects within the kidney.
在兔肾髓质微粒体中研究了13-氢过氧十八碳二烯酸（13-HPODE）对前列腺素（PGs）合成的影响。将髓质微粒体与花生四烯酸在含有还原型谷胱甘肽和对苯二酚的0.1M- Tris/HCl缓冲液（pH 8.0）中孵育，使用9-蒽基重氮甲烷进行衍生化，通过高压液相色谱法测定生成的前列腺素E2（PGE2）、前列腺素F2α（PGF2α）和前列腺素D2（PGD2）。在我们的孵育条件下，发现兔肾髓质主要产生PGE2。添加13-HPODE对所有三种前列腺素的产生均有相似程度的抑制作用。13-羟基十八碳二烯酸并未抑制前列腺素的形成，这表明13-HPODE对前列腺素形成的抑制作用需要氢过氧基部分。利用天然脂肪酸亚油酸和叔丁基过氧化氢进行的实验表明，脂肪酸衍生的氢过氧化物在肾髓质前列腺素合成中具有重要作用。我们得出结论，13-HPODE是肾髓质环氧化酶的抑制剂，可能在肾脏内具有功能作用。
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