双苯氟嗪对局灶性脑缺血再灌注损伤的保护作用(英文)  

Protective effect of dipfluzine on focal cerebral ischemia-reperfusion injury

作　　者：梅和珊[1] 苏素文[1] 李军霞[1] 李海芳[1] 王永利[1] 

机构地区：[1]河北医科大学药理学教研室,河北石家庄050017

出　　处：《中国药理学与毒理学杂志》2004年第5期333-337,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家高技术研究发展计划 (86 3计划 )资助项目 (2 0 0 2AA2Z3132 )~~

摘　　要：目的　评价双苯氟嗪 (Dip)和氟桂利嗪 (Flu)在大鼠局灶性脑缺血再灌注模型中的神经保护作用。方法　将内皮素 1(ET 1)灌注到大脑中动脉附近制备大鼠局灶性脑缺血再灌注模型 ,并于灌注ET 1后 30min和 4 .5h腹腔注射溶剂、Dip 10 ,2 0和4 0mg·kg- 1和Flu 2 0mg·kg- 1,采用氢清除法监测灌注ET 1前、后纹状体血流变化 ,并对缺血后 2 4h脑梗塞面积、血清中超氧化物歧化酶 (SOD)活性和丙二醛 (MDA)含量的变化进行了测定。结果　Dip 2 0和 4 0mg·kg- 1于灌注ET 1后 70和 10 0min明显改善缺血侧纹状体血流量下降 ;Flu 2 0mg·kg- 1的作用较弱 ,仅于灌注ET 1后 10 0min明显改善缺血侧纹状体血流量 ;Dip可以剂量依赖性的降低脑梗塞面积 (r =0 .9797,P <0 .0 1) ,同剂量Flu可产生相似的作用 ;各剂量组Dip和Flu均可增加血清中SOD活性、降低MDA含量。结论　Dip和Flu对脑缺血再灌注损伤有明显的保护作用 ,Dip改善脑血流的作用略强于Flu ,其保护作用的机制与改善脑血流和抗氧化作用有关。AIM To compare the protective effects of dipfluzine (Dip) an d flunarizine (Flu) on the focal cerebral ischemia-reperfusion injury in rats. METHODS Endothelin-1(ET-1) was perfused to the proximity of the middle cerebral artery (MCA) to induce focal cerebral ischemia-reperfusion model. Solvent, Dip 10, 20 and 40 mg·kg -1 and Flu 20 mg·kg -1 were given ip 30 min and 4.5 h after ET-1 perfusion. The changes in cerebral blood flow (CBF) in striatum before and after ET-1 perfusion were characterized using hydrogen clearance technique. The infarct volume, the activity of superoxide di smutase(SOD)and the content of malondialdehyde(MDA)in serum were measured re spectively at 24 h after ET-1 application to evaluate the effects of Dip an d Flu. RESULTS Dip 20 and 40 mg·kg -1 significantly alleviate d the CBF decrease at 70 and 100 min after ET-1 perfu- sion, but Dip 10 mg·kg -1 did not. Flu 20 mg·kg -1 could enhance CBF only at 100 min, which showed relative weak effect on CBF. A significant reductions in infarct volume were found in Dip-treated groups as well as in Flu-treated group compared with the solvent group, and Dip showed a dose-dependent reduction(r=0.9797, P<0.01). Furthermore, Dip and Flu also raised SOD activity and decrea sed MDA content in serum. CONCLUSION Dip and Flu showed significant protective effects against cerebral ischemia-reperfusion injury via increasing CBF in ischemic-regions and their antioxidant activity. Di p showed a relatively stronger effect than Flu in improving CBF.

关 键 词：钙通道阻滞剂 双苯氟嗪 氟桂利嗪 内皮素-1 脑缺血 自由基类 氢清除法 

分 类 号：R96[医药卫生—药理学]