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探讨了皮质酮对原代培养海马神经细胞的毒性作用及作用机理.结果显示,无血清培养基中加入皮质酮(10nmol·L-1-0.1mmol·L-1)可浓度依赖地损伤原代培养的海马和皮层神经细胞,其EC50分别为3.2和85μmol·L-1.预先加入N-甲基-D-天冬氨酸(NMDA)受体拮抗剂地佐环平(MK-801,终浓度为50μmol·L-1)可显著拮抗皮质酮(10μmol·L-1)对海马神经细胞的毒性作用.皮质酮同海马脑薄片共同孵育10和20min可明显增加海马脑薄片谷氨酸和谷氨酰胺的释放,对天冬氨酸的释放则无明显影响.实验结果提示,皮质酮可选择性地损伤原代培养海马神经细胞,该毒性作用可能与其增加兴奋性氨基酸释放有关.
To explore the corticosterone primary cultured hippocampal neuronal toxicity and mechanism of action. The results showed that cortisone (10 nmol·L-1-0.1 mmol·L-1) in serum-free medium could damage the primary cultured hippocampal and cortical neurons in a concentration-dependent manner with EC50 of 3.2 and 85 μmol · L-1. MK-801 (50μmol·L-1) preconditioned with N-methyl-D-aspartate (NMDA) antagonist significantly antagonized corticosterone (10μmol·L-1) Toxicity to hippocampal neurons. Incubation of corticosterone with hippocampal slices for 10 and 20 min significantly increased glutamate and glutamine release in the hippocampal slices without any significant effect on the release of aspartic acid. Experimental results suggest that corticosterone can selectively damage primary cultured hippocampal neurons, which may be related to the increase of excitatory amino acid release.