Domenici M R, Longo R, de Carolis A S, Frank C, Sagratella S
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Roma, Italy.
Eur J Pharmacol. 1993 Mar 23;233(2-3):291-3. doi: 10.1016/0014-2999(93)90064-o.
The effects of the 21-aminosteroids, U-74500A and U-78517F (drugs endowed with lipid peroxidation inhibitor properties) were tested on hypoxia-induced functional failure in rat hippocampal slices. For comparison, the effects of the non-competitive N-methyl-D-aspartate antagonist, dizocilpine (MK-801) were studied. Perfusion of slices with 50 microM of MK-801 or with 50-100 microM of U-78517F, but not with 100-200 microM of U-74500A, significantly (P < 0.01) increased the incidence of reappearance of the CA1 population spikes after reoxygenation in rat hippocampal slices subjected to a 45-min hypoxic period followed by a 45-min reoxygenation period. Perfusion of slices with 12.5 microM of MK-801 plus 12.5 microM of U-78517F significantly (P < 0.05) increased the incidence of reappearance of the CA1 population spikes after reoxygenation with respect to perfusion of slices with 12.5 microM of U-78517F alone or with 12.5 microM of MK-801 alone. The results show that 21-aminosteroids have protective effects against hypoxia-induced functional failure in rat hippocampal slices. In addition, the data show that, under the same experimental conditions, the NMDA receptor antagonist, MK-801, was also able to improve hypoxia-induced functional failure. On the whole, the results suggest that the hypoxia-induced functional electrical failure might depend on both release of excitatory amino acids and oxygen free-radical-mediated membrane lipid peroxidation.
对21 -氨基类固醇U - 74500A和U - 78517F（具有脂质过氧化抑制特性的药物）对大鼠海马切片缺氧诱导的功能衰竭的影响进行了测试。作为比较，研究了非竞争性N -甲基- D -天冬氨酸拮抗剂地佐环平（MK - 801）的作用。用50微摩尔/升的MK - 801或50 - 100微摩尔/升的U - 78517F灌注切片，但不是用100 - 200微摩尔/升的U - 74500A，显著（P < 0.01）增加了在经历45分钟缺氧期后再进行45分钟复氧的大鼠海马切片复氧后CA1群体峰电位再次出现的发生率。用12.5微摩尔/升的MK - 801加12.5微摩尔/升的U - 78517F灌注切片，相对于单独用12.5微摩尔/升的U - 78517F或单独用12.5微摩尔/升的MK - 801灌注切片，显著（P < 0.05）增加了复氧后CA1群体峰电位再次出现的发生率。结果表明，21 -氨基类固醇对大鼠海马切片缺氧诱导的功能衰竭具有保护作用。此外，数据表明，在相同的实验条件下，NMDA受体拮抗剂MK - 801也能够改善缺氧诱导的功能衰竭。总体而言，结果表明缺氧诱导的功能性电衰竭可能既取决于兴奋性氨基酸的释放，也取决于氧自由基介导的膜脂质过氧化。
