Nifedipine对缺血突触体游离钙和氨基酸释放的影响

Effects of nifedipine on the level of free calcium and release of amino acids from ischemic synaptosomes

目的：通过Nifedipine对缺血突触体内游离钙浓度及氨基酸释放量的影响，初步探讨其脑缺血保护作用与兴奋性氨基酸（EAA）和抑制性氨基酸（IAA）释放关系。方法：营养液中去除糖和氧建立大鼠脑突触体缺血模型，检测静息及高钾去极化状态下缺血突触体游离钙浓度及EAA和IAA释放量的变化，并检测Nifedipine对此变化的影响。结果：大鼠突触体缺血状态致游离钙浓度、门冬氨酸和甘氨酸、牛磺酸、γ-氨基丁酸释放量明显增加，而谷氨酸亦有增加趋势。缺血 + 50 mmol/L 高钾刺激后，游离钙浓度及上述EAA及IAA释放量均进一步增加。10-4 mol/L Nifedipine可明显降低两种状态下缺血突触体内游离钙浓度，同时亦显著阻遏静息状态缺血突触体IAA的释放及去极化状态EAA和IAA的释放。结论：Nifedipine的抗脑缺血致脑损伤作用主要与其对抗缺血引起的突触体内游离钙浓度升高有关，其抑制EAA和IAA释放与脑缺血保护作用的关系有待进一步研究。

Objective：The effects of nifedipine on the release of amino acids and free calcium concentrations ([Ca2+ ]i) from ischemic synaptosomes were investigated in order to explore the relationship between its protective action against brain injury induced by ischemia and its influence on [Ca2+ ]i as well as release of excitatory amino acids (EAA) and inhibitory amino acids (IAA). Methods：Ischemic synaptosome model was established by substration of glucose and oxygen from synaptosome suspension. The release of EAA, IAA and [Ca2+ ]i from or in ischemic synaptosomes were determined under the conditions of either resting or stimulation of 50 mmol/L K+. Results: Ischemic condition induced [Ca2+ ]i increase in both resting and 50mmol/L K+- stimulated synaptosomes. Obviously it caused more release of aspartate, glutamate, glycine, taurine, GABA from 50 mmol/L K+- stimulated synaptosomes than resting synaptosomes. 10-4 mol/L nifedipine not only reduced the [Ca2+ ]i increase, but also decreased the release of aspartate, glutamate, and glycine, taurine, GABA in ischemic synaptosomes. Conclusion：The neuronal protection of nifedipine against brain damage induced by ischemia is related to inhibiting calcium influx. However, whether the protective effect of nifedipine is related to simultaneously blocking release of EAA and IAA needs further illustration.