Bergasa N V, Vergalla J, Cole K E, Wahl L M, Jones E A
Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Gastroenterol Hepatol. 1992 Nov-Dec;7(6):608-13. doi: 10.1111/j.1440-1746.1992.tb01494.x.
The hepatocellular cytoprotective effects of 16,16-dimethyl prostaglandin E2 (dmPGE2), an analogue of PGE2, were investigated using primary cultures of rat hepatocytes and aflatoxin B1 as the hepatotoxin. Lactic dehydrogenase (LDH) release by hepatocytes was used as an index of hepatotoxicity. When aflatoxin-treated hepatocytes were co-cultured with 16,16-dmPGE2 (0.01-0.5 micrograms/mL) LDH release was significantly reduced and ultrastructural changes of hepatocellular injury were markedly diminished. The magnitude of the cytoprotective effect was not dependent on the concentration of the prostaglandin over the range tested. A significant cytoprotective effect was also induced when hepatocellular cyclic AMP (cAMP) levels were increased by the addition of dibutyl-cAMP. In contrast to 16,16-dmPGE2, PGF2 alpha Tromethamine, an analogue of PGF2 alpha, which does not stimulate cAMP, induced insignificant changes in cytoprotection. These findings indicate that only a low concentration of 16,16-dmPGE2 (> or = 0.01 micrograms/mL) is necessary to induce a maximal hepatocellular cytoprotective effect and suggest that this effect may be dependent on activation of cAMP.
以大鼠原代肝细胞为实验对象，黄曲霉毒素B1为肝毒素，研究了前列腺素E2类似物16,16-二甲基前列腺素E2（dmPGE2）的肝细胞保护作用。肝细胞释放的乳酸脱氢酶（LDH）用作肝毒性指标。当用黄曲霉毒素处理过的肝细胞与16,16-dmPGE2（0.01 - 0.5微克/毫升）共培养时，LDH释放显著减少，肝细胞损伤的超微结构变化明显减轻。在所测试的浓度范围内，细胞保护作用的程度不依赖于前列腺素的浓度。当通过添加二丁酰环磷腺苷（dibutyl-cAMP）使肝细胞环磷腺苷（cAMP）水平升高时，也诱导出显著的细胞保护作用。与16,16-dmPGE2相反，不刺激cAMP的前列腺素F2α类似物曲美他明（PGF2 alpha Tromethamine）诱导的细胞保护作用变化不显著。这些发现表明，仅需低浓度的16,16-dmPGE2（≥0.01微克/毫升）即可诱导最大的肝细胞保护作用，并提示这种作用可能依赖于cAMP的激活。
