谷氨酸转运体靶点药物的抗脑缺血作用研究进展  

Drugs targeting glutamate transporters for prevention and treatment of cerebral ischemia

作　　者：黄龙飞[1] 钱贻崧[1] 关腾[1] 黄梦昊[1] 李运曼[1] 

机构地区：[1]中国药科大学生理教研室,南京210009

出　　处：《中国新药杂志》2012年第4期390-395,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金面上项目(30672523);国家自然科学基金重大研究计划(培育项目)(90713037);教育部科技创新工程重大项目培育基金(706030);高等学校博士学科点专项科研基金和中国药科大学硕士基金(ZJ10097)

摘　　要：兴奋性氨基酸毒性是脑缺血损伤的主要机制之一。缺血期间谷氨酸的大量累积会导致神经元细胞、星形胶质细胞等神经细胞发生兴奋性毒性损伤,因此对缺血期间谷氨酸水平的调控一直是脑缺血防治药物研究的重点。近年来研究表明,通过上调星形胶质细胞上谷氨酸转运体GLAST(EAAT1)和GLT-1(EAAT2)的表达或活性,增加缺血时谷氨酸的摄取,维持突触间隙内谷氨酸的正常浓度,从而降低兴奋性毒性,减轻缺血性脑损伤。一些化合物如β-内酰胺类抗生素、尿酸、甲状腺激素、雌激素、山楂酸等已在体内或体外实验中被证实对谷氨酸转运体的调节作用,对抗谷氨酸毒性,发挥神经保护作用。研究和开发以星形胶质细胞谷氨酸转运体为作用靶点的药物,为缺血性脑损伤的预防和治疗提供了一条新的途径。Glutamate is the most important excitatory neurotransmitter in the brain.However,it is a potent neurotoxin and is considered as the primary cause of neuron death during acute brain ischemia and in neurodegenerative diseases.Thus,the effective treatment of excitotoxic injury requires modulation of glutamate release,glutamate receptor activation,ROS generation and glutamate transport.The astrocytic glutamate transporters GLAST/EAAT1 and GLT-1/EAAT2 are crucial for removal of glutamate from the synaptic cleft,and are essential for maintaining a low concentration of extracellular glutamate in the brain.Enhanced transporter expression or activity is neuroprotective.Some compounds,such as β-lactams,uric acid,thyroid hormone,estrogen and maslinic acid,have been indicated to reduce the neuron injury after cerebral ischemia by regulation of glutamate transporter function.Researches on astrocytic glutamate transporter-dependent neuroprotection provide a novel strategy for cerebral ischemia therapy and drug development.

关 键 词：脑缺血 GLAST GLT-1 五环三萜 

分 类 号：R966[医药卫生—药理学]