依达拉奉、米诺环素及ONO-1078对缺氧缺糖诱导大鼠海马脑片电生理改变的作用  

Effects of edaravone, minocycline and ONO-1078 on oxygen/glucose deprivation-induced electrophysiological alteration in rat hippocampal slices

作　　者：李伟 魏尔清[1] 王梦令[1] 刘路英[1] 

机构地区：[1]浙江大学医学院药理学教研室,浙江杭州310031

出　　处：《药学学报》2004年第2期81-84,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30 2 71 498);浙江省自然科学基金资助项目(3990 90 )

摘　　要：目的　建立离体海马脑片缺氧缺糖 (OGD)电生理变化模型 ,观察依达拉奉、米诺环素和ONO 10 78{pranlukast,4 氧 8 [对 (4 苯丁氧基 )苯甲酰氨基 ] 2 (5 四氮基 ) 4H 1 苯并吡喃半水化合物 }的神经保护作用。方法大鼠海马脑片以无氧无糖处理 ,记录脑片群峰电位 (PS) ,部分实验以TTC染色观察脑片活性。结果　OGD处理 4min为最佳损伤条件 ,1h后可恢复至基础水平的 (2 9± 6) %。自由基清除剂依达拉奉 (1和 10 μmol·L- 1)明显增强PS波的恢复 ;抗炎药米诺环素 (10 μmol·L- 1)和白三烯受体拮抗剂ONO 10 78(1μmol·L- 1)无显著恢复作用 ;阳性对照药氯胺酮也浓度依赖性促进PS恢复。结论　 4minOGD为离体海马脑片缺血电生理变化的可行模型 ;依达拉奉对OGD脑片损伤有浓度依赖性保护作用 ,而米诺环素和ONO 10Aim To establish an in vitro model of hippocampal slice to detect electrophysiol ogical alteration after oxygen/glucose deprivation (OGD), and to observe the eff ects of edaravone, minocycline and ONO-1078 {pranlukast, 4-oxo-8-[p-(4 -phenylbutyloxy) benzoyl-amino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemi hydrate}. Methods Hippocampal slices from rats were perfused with artificial cerebrospinal fluid l acking oxygen and glucose for 3, 4, 7 and 10 min. The population spike (PS) was recorded, and 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed in some experiments, to detect the slice viability in the presence or absence of drugs in the perfusion solution. Results Four min of OGD treatment was the most suitable duration for induction of slice injury, and PS amplitudes were recovered to (29±6)% of baseline values within 1 h after 4 min OGD. Edaravone, a free radical scavenger, at 1 and 10 μmol·L -1 significantly increased the recovery rate to (56±13)% and (69±12)% of baseline respectively 1 h after OGD. However, the anti-inflammatory drug min ocycline (10 μmol·L -1 ) and leukotriene receptor antagonist ONO-1078 (1 μmol·L -1 ) did not increase the recovery. NMDA receptor antagonis t ketamine, as a positive control, also promoted the recovery concentration-dep endently. Conclusion OGD for 4 min was a feasible in vitro ischemia model for determination on el ectrophysiological alteration in hippocampal slices. Edaravone showed concentrio n-dependent protective effect on OGD injury, and anti-inflammatory drugs m inocycline and ONO-1078 showed no effect.

关 键 词：依达拉奉 米诺环素 ONO-1078 海马脑片 缺氧缺糖 电生理学 神经保护 

分 类 号：R971[医药卫生—药品]