丁基苯酞对低糖低氧引起神经细胞内钙升高的作用

目的:探讨抗脑缺血新药丁基苯酞(NBP) 对脑缺血过程中细胞内游离钙升高的影响及其作用机制。方法:采用低糖低氧损伤胎鼠或新生鼠神经细胞以模拟脑缺血,用Fura-2/AM 作荧光指示剂,观察手性丁基苯酞对神经细胞内游离钙升高的抑制作用,并用内钙释放剂thapsigargin,外源性谷氨酸,高K+ 及钙离子载体A23187 作工具药,对其作用环节进行分析。结果:d-,l-,dl-丁基苯酞能完全抑制低糖低氧造成的神经细胞内钙升高。手性NBP能降低thapsigargin 引起的内质网钙库释放,d-NBP 还对谷氨酸引起的内钙升高表现出抑制作用。结论:丁基苯酞抑制低糖低氧条件下神经细胞内钙升高的作用环节主要是抑制细胞内钙库的释放。

EFFECTS OF 3-n-BUTYLPHTHALIDE ON THE INCREASE OF INTRACELLULAR CALCIUM IN NEURONS SUBJECTED TO HYPOXIA AND HYPOGLYCEMIA AND ITS MECHANISMS

AIM: To study the decreasing effects and the mechanisms of d , l and dl butylphthalide (NBP) on intracellular calcium ([Ca 2 ]i) in neurons subjected to hypoxia and hypoglycemia. METHODS: Neurons were prepared from fetal or newborn rat brain and Fura 2/AM was used as fluorescence indicator to study the actions of NBP on [Ca 2 ]i. Thapsigargin, glutamine, KCl or calcium ionpore A23187, which can induce increase of intracellular calcium, were used as tool drugs to analyze the mechanisms of the action of chiral NBP. RESULTS: d , l and dl NBP were shown to significantly inhibit the increase of intracellular calcium caused by hypoxia and hypoglycemia. However, chiral NBP was found to have no effect on the increase of [Ca 2 ]i induced by the tool drugs except thapsigargin. d NBP seemed to have some decreasing effect on glutamate. CONCLUSION: The actions of d , l and dl NBP might be mediated mainly by its decreasing effect on the release of calcium from intracellular calcium pool.