粉防己碱对体外培养大鼠脑皮层神经元损伤的保护作用

兴奋性氨基酸类神经毒剂与粉防己碱(Tet)共同作用于原代培养胎鼠大脑皮层神经元24h,发现10^-7,10^-6mol·L^-1Tet明显降低谷氨酸(Glu),β-N-oxalylamino-L-alanine(BOAA)和β-N-methylamino-L-alanine(BMAA)导致的培养液乳酸脱氢酶(LDH)活性增高,细胞形态损害减轻,细胞数量增加。对NMDA介导的神经元损伤改变无影响。提示Tet对某些Glu类神经毒剂引起的胎鼠大脑皮层神经元损伤有一定保护作用,其机制可能是抑制细胞膜Na⁺通道开放,阻止膜去极化而影响电压依赖性Ca²⁺通道启动。对NMDA受体可能亦有一定作用。

PROTECTIVE EFFECT OF TETRANDKINE ON NEURONAL INJURY IN CULTURED CORTICAL NEURONS OF RATS

The ability of tetrandrine (Tet),as a Ca²⁺ antagonist isolated from a traditionalChinese herb,to reduce cortical neuronal injury was quantitatively examined in cell cultures derivedfrom fetal rats by measurement of lactate dehydrogenase(LDH)released to the extracellular bathingmedia.Cell cultures exposed to excitotoxins-glutamate(Glu),N-methyl-D-aspartate(NMDA),β-N-oxalylamino-L-alanine(BOAA, on non-NMDA receptors)and β-N-methylamino-L-alanine(BMAA,on NMDA receptors)-for 24 h showed widespread neuronal injury, which was subetantially attenuatedby addition of Tet 10^-7～100^-6mol·L^-1 except to NMDA,Tet failed to protect neurons againstNMDA. These resuIts suggest that Tet has protective effect on fetal rat corticaI neuronal injuryinduced by some excitotoxins in vitro,The mechanism of action was hypothesized that opening of Ca²⁺ channel in cellular membrane would not happen,beeause of inhibition of Na⁺ influx and membranedepolarization induced by Tet.As a result, cytosolic free Ca²⁺ overload and then neuroal injury wereprevented or lightened.