Forloni G, Angeretti N, Smiroldo S
Unit of Neurobiology of Alzheimer, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
J Neurosci Res. 1994 Jan;37(1):92-6. doi: 10.1002/jnr.490370112.
The neuroprotective properties of acetyl-L-carnitine (ALCAR) were investigated in primary cell cultures from rat hippocampal formation and cerebral cortex of 17-day-old rat embryos. Chronic exposure to ALCAR (10-50 microM for 10 days) reduced the cell mortality induced by 24 hr fetal calf serum deprivation. Protection was partial when the neuronal cells, chronically treated with ALCAR (50 microM), were exposed to glutamate (0.25-1 mM) and kainic acid (250-500 microM) for 24 hr. The neurotoxicity induced by N-methyl-D-aspartate (NMDA, 250 microM) was attenuated by the acute co-exposure with ALCAR (1 mM), the chronic treatment with ALCAR (50 microM) significantly reduced the neuronal death induced by NMDA (0.25-1 mM). Cell mortality was also investigated in ALCAR-treated hippocampal cultures chronically treated with beta-amyloid fragment 25-35. ALCAR appeared to have neuroprotective activity. This suggests an explanation of the positive results obtained with ALCAR in the treatment of Alzheimer's disease.
在来自17日龄大鼠胚胎海马结构和大脑皮层的原代细胞培养物中研究了乙酰-L-肉碱(ALCAR)的神经保护特性。长期暴露于ALCAR(10 - 50微摩尔,持续10天)可降低24小时胎牛血清剥夺诱导的细胞死亡率。当用ALCAR(50微摩尔)长期处理的神经元细胞暴露于谷氨酸(0.25 - 1毫摩尔)和海藻酸(250 - 500微摩尔)24小时时,保护作用是部分性的。N-甲基-D-天冬氨酸(NMDA,250微摩尔)诱导的神经毒性通过与ALCAR(1毫摩尔)急性共同暴露而减弱,用ALCAR(50微摩尔)长期处理可显著降低由NMDA(0.25 - 1毫摩尔)诱导的神经元死亡。在用β-淀粉样蛋白片段25 - 35长期处理的ALCAR处理的海马培养物中也研究了细胞死亡率。ALCAR似乎具有神经保护活性。这为在阿尔茨海默病治疗中用ALCAR获得的阳性结果提供了解释。