caspase-3抑制药和钙拮抗药联合应用对氧糖剥夺性神经元缺血损害的保护作用  

Protective effects of combined caspase-3 inhibitor and calcium antagonist on oxygen glucose deprivation-induced ischemic neuronal injury

作　　者：张拥波[1] 董为伟[2] 王得新[1] 

机构地区：[1]首都医科大学附属北京友谊医院神经内科,100050 [2]重庆医科大学附属第一医院神经内科

出　　处：《中国现代神经疾病杂志》2007年第1期57-60,共4页Chinese Journal of Contemporary Neurology and Neurosurgery

基　　金：国家自然科学基金重点项目(39730170)

摘　　要：目的探讨半胱氨酸天冬氨酸蛋白酶-3(caspase-3)抑制药Ac-DEVD-CHO与钙拮抗药尼莫地平对神经元缺血性损害的协同保护作用。方法利用新生(<24 h)Wistar大鼠皮质基底节神经元进行原代分散培养,建立氧糖剥夺离体神经元“缺血”模型,采用乳酸脱氢酶测定法评价培养神经元的损害程度;并通过荧光免疫吸附酶法检测caspase-3活性,观察caspase-3抑制药Ac-DEVD-CHO(0．50μg／ml)、钙拮抗药尼莫地平(20μmol／L)及二者联合应用对氧糖剥夺4 h神经元损害和caspase-3活性的影响。结果Ac-DEVD-CHO、尼莫地平及二者联合用药均可显著减轻氧糖剥夺4h后的神经元损害,并可抑制caspase-3活性的升高,与氧糖剥夺对照组比较差异有统计学意义(P<0．01);两药联合应用具有明显协同作用。结论caspase-3抑制药与钙拮抗药对缺血性神经元具有协同保护作用。Objective To test the synergetic protective effects of combined cysteine asparate protease-3 （caspase-3） inhibitor Ac-DEVD-CHO and calcium antagonist nimodipine on isehemic neuronal injury in vitro model. Methods Primary neuronal cultures derived from cortex basal ganglion of neonatal Wistar rats （〈24h） and kept in culture for 14 days, and then exposed to oxygen glucose deprivation （OGD） to establish isolated ＂ischemic＂ neuronal model. The neuronal injury was measured by lactic dehydrogenase （LDH） activity assay after 24h. The caspase-3 activity was determined with fluorometric immunosorbent enzyme assay （FIENA）. Observed the effect of Ac-DEVD-CHO （0.50 μg/ml）, nimodipine （20 μmol/L） and combined treatment on neuronal injury and caspase-3 activity, respectively, after 4 h of OGD. Results In comparison with OGD control group, Ac-DEVD-CHO, nimodipine, and combined treatment groups all significantly reduced the 4 h-OGD-induced neuronal injury and inhibited the increase of caspase-3 activity （P〈 0.01）. Combined treatment produced significantly synergetic effects on ischemic neuronal injury. Conclusion Caspase- 3 inhibitor Ac-DEVD-CHO and calcium antagonist nimodipine could cause pronounced synergetic neuroprotection.

关 键 词：神经元 细胞 培养的 钙 半胱氨酸蛋白酶类 半胱氨酸蛋白酶抑制剂 尼莫地平 

分 类 号：R744[医药卫生—神经病学与精神病学]