(-)-S·R-蝙蝠葛苏林碱对谷氨酸引起的大鼠大脑皮质神经元损伤的保护作用

用细胞培养方法,在原代培养的大鼠皮质神经细胞上,观察了(-)-S·R-蝙蝠葛苏林碱对谷氨酸引起的神经元损伤的保护作用。以Fura-2/AM为Ca²⁺的荧光指示剂,用AR-CM-MIC阳离子测定系统观察(-)-S·R-蝙蝠葛苏林碱对谷氨酸诱发大鼠脑皮质神经细胞内Ca²⁺升高的影响。结果表明(-)-S·R-蝙蝠葛苏林碱能剂量依赖性地抑制谷氨酸的神经毒作用,对谷氨酸诱发的神经细胞内游离Ca²⁺升高有明显的抑制作用。提示蝙蝠葛苏林碱对缺血性脑损伤有保护作用。

Protective effects of (-)-S.R-daurisoline on neuronal injury in rat primary cortical cultures]

The neuroprotective effects of (-)-S.R-daurisoline on glutamate-induced neurotoxicity were studied in rat primary cortical cultures. The inhibitory effects of (-)-S.R-daurisoline on glutamate-elicited free intracellular Ca2+ increase were also studied in freshly dissociated single brain cells isolated from new born rat using AR-CM-MIC Cation Measurement System. Our experimental results demonstrated that (-)-S.R-daurisoline could obviously inhibit the neurotoxicity induced by glutamate and significantly increased cell viability in dose-dependent manner. In inhibiting glutamate-induced neurotoxicity, the IC50 value of (-)-S.R-daurisoline was found to be 3.4 mumol.L-1. (-)-S.R-daurisoline was also shown to markedly inhibit glutamate-elicited increase of cytosolic free Ca2+ concentration in dose-dependent manner with IC50 value of 2.0 mumol.L-1. Our results showed that (-)-S.R-daurisoline has an obvious protective effect on glutamate-induced neurotoxicity in primary cortical cultures. The protective mechanism of (-)-S.R-daurisoline may be relevant to inhibit Ca2+ influx into cells via glutamate-mediated ligand-gated ion channels.