摘要
目的 初步探讨地佐环平 (MK 80 1)对脑缺血的保护作用与兴奋性氨基酸 (EAA)和抑制性氨基酸(IAA)释放的关系。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EAA和IAA释放量及游离钙浓度。结果 大鼠突触体缺血状态致天冬氨酸和甘氨酸、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 + 5 0mmol·L- 1K+刺激后 ,上述EAA及IAA释放量均进一步增加。静息及去极化状态下的缺血突触体游离钙浓度显著增加。MK 80 10 .1mmol·L- 1可显著阻遏静息及去极化状态缺血突触体释放EAA及IAA ,但对EAA的抑制作用更明显 ;同时亦明显降低两种状态下缺血突触体内游离钙浓度。结论 MK 80 1的抗脑缺血致脑损伤作用 ,至少部分与其对抗缺血引起的突触体内游离钙浓度升高和EAA释放量增加的作用有关。
AIM To explore whether the influence of dizocilpine(MK 801) on release of inhibitory amino acids(IAA) contributes to its neuroprotection against ischemic injury. METHODS Ischemic synaptosome model was established by subtraction of glucose and oxygen from synaptosome suspension. The release of excitatory amino acid(EAA) and IAA, and [Ca 2+ ] i from ischemic synaptosomes were determined under the conditions of either resting or stimulation of 50 mmol·L -1 K +. RESULTS Ischemic condition more obviously caused increasing release of aspartate, glutamate, glycine, taurine, GABA from 50 mmol·L -1 K + stimulated synaptosomes than resting synaptosomes. It also induced [Ca 2+ ] i increase in both resting and 50 mmol·L -1 K + stimulated synaptosomes. MK 801 0.1 mmol·L -1 not only blunted the [Ca 2+ ] i increase, but also more significantly decreased the release of aspartate and glutamate in ischemic synaptosomes, compared with decreasing release of glycine, taurine and GABA under same conditions. CONCLUSION The neuronal protection of MK 801 against brain damage induced by ischemia at least partly related to inhibition of calcium influx and more obvious block of EAA release from ischemic synaptosomes than that of IAA.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2002年第3期161-164,共4页
Chinese Journal of Pharmacology and Toxicology
基金
TheprojectsupportedbytheCommitteeofEducationofSichuanProvince(95 0 0 4 )
关键词
地佐环平
突触体
氨基酸释放
游离钙
脑缺血
cerebral ischemia
synaptosomes
dizocilpine
calcium, cytosolic
amino acids
