皮质酮对大鼠原代海马神经细胞的毒性作用  

NEUROTOXIC EFFECT OF CORTICOSTERONE ON PRIMARY CULTURED HIPPOCAMPAL CELL

作　　者：周建政[1] 张永祥[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国神经科学杂志》1998年第1期11-15,共5页

摘　　要：本文探讨了皮质酮（corticosterone，CORT）对大鼠原代海马神经细胞的毒性作用及作用机制。实验结果显示，CORT加入无血清DMEM培养基可剂量依赖地损伤原代培养海马神经细胞，LD50为3．2×10－6mol／L，而原代培养的皮层神经细胞只被高浓度皮质酮（10－5mol／L和10－4mol／L）所损伤，其LD50为8.5×10－5mol／L，比前者大近20倍。原代培养的海马神经细胞补充高浓度的葡萄糖或NMDA一受体拮抗剂MK－801可显著地拮抗CORT对海马神经细胞的毒性作用。同时，CORT处理的海马神经细胞胞内ATP水平明显降低，而补充高浓度葡萄糖（25mmol／L）可逆转CORT诱导的ATP耗竭。以上结果提示，CORT可选择地损伤海马神经细胞，这一损伤作用与葡萄糖浓度相关。实验结果进一步提示，CORT对海马神经细胞的毒性作用可能与其导致的能量水平低下和兴奋性氨基酸的堆积有关．The neurotoxic effect of corticosterone (CORT) on primary cultured hippocampal neuronsand itS underlying mechanism were investigated. The present results indicated that supplementation withCORT to serum-free DMEM culture dose-dependently decreased the survival of hippocampal neurons with aLD50 of 3. 2× 10-6 mol/L. In contrast, cerebral neurons were affected only by high concentrations of CORT(10-5 mol/L and 10-4mol/L) with the LD50 of 8. 5 × 10-5 mol/L, 20 times larger than the former. Supplmentation with both high concentration of glucose(25 mmol/L) and NMDA-receptor antagonist, MK-801(5×10-5mol/L)significantly ameliorated the neurotoxic efrect of CORT on hippocampal neurons. Meanwhile,CORT treatment markedly reduced the intracellular ATP content of hippocampal neurons and supplementation with high concentration of glucose (25 mmol/L) to the culture reversed the intracellular ATP depletioninduced by CORT. The results suggested that CORT preferentially injured the primary cultured hippocampalcell and neurotoxic effect of CORT on hippecampal neurons might be related to energy dericiency and excitatory amino acid accumulation.

关 键 词：皮质酮 海马 皮层 兴奋性氨基酸 

分 类 号：R977.11[医药卫生—药品] R338[医药卫生—药学]