咯利普兰对局灶性脑缺血-再灌注损伤大鼠学习记忆及海马PDE4活性的影响  

Effects of rolipram on learning and memory and the activity of PDE4 in hippocampus following the focal brain injury induced by ischemia-reperfusion in rats

作　　者：刘旭[1] 程玉芳[1] 张汉霆[1] 徐江平[1] 

机构地区：[1]南方医科大学药学院药理学系,广东广州510515

出　　处：《中国病理生理杂志》2008年第6期1096-1100,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No30672453);广州省自然科学基金重点资助项目(No7117782)

摘　　要：目的:观察咯利普兰对局灶性脑缺血-再灌注损伤大鼠学习记忆能力及海马PDE4活性的影响。方法:采用线栓法阻断大鼠大脑中动脉制备局灶性脑缺血-再灌注损伤模型,将大鼠随机分成假手术组、模型组和咯利普兰治疗组(1mg.kg-1),术后6h腹腔注射首次给药,连续2周。通过水迷宫和避暗实验测试其学习记忆水平,且应用高效液相法(HPLC)检测大鼠海马组织PDE4活性。结果:水迷宫测试中,与假手术组相比,模型组的寻台时间和游泳距离显著增加(P<0.05),与模型组比较,咯利普兰治疗组寻台时间和游泳距离显著缩短(P<0.05);在避暗测试中,模型组的平均潜伏期比假手术组显著减少(P<0.01),错误次数显著增加(P<0.05),与模型组比较,咯利普兰治疗组的平均潜伏期显著增加(P<0.05),错误次数也明显减低;HPLC检测结果显示:模型组大鼠海马组织PDE4活性显著升高(P<0.01);咯利普兰组大鼠海马组织PDE4活性明显降低(P<0.05)。结论:咯利普兰能降低局灶性脑缺血-再灌注损伤大鼠海马PDE4活性,并减弱局灶性脑缺血-再灌注大鼠的学习记忆功能障碍。AIM ： To investigate the effects of rolipram on the ability of learning and memory and the activity of PDE4 in hippocampus following the focal brain injury induced by ischemia- reperfusion in rats. METHODS： The cerebral ischemia-reperfusion injury model was made by middle cerebral artery occlusion （MCAO） in rats. The rats were randomly divided into sham-operated group, model group, and rolipram group. Rolipram was administered once a day （ 1 mg/kg, ip） from 6 h after the onset of the operation for 2 weeks. Then the learning and memory abilities were tested after Morris water maze and step - though training. The activity of PDE4 in hippocampus was evaluated by HPLC. RESUETS： In the Morris water maze test, compared to sham -operated group, the platform-finding time and swimming distance in model group were significantly longer （ P 〈 0. 05 ）. Compared to model group, the platform-finding time and swimming distance in rolipram group were significantly shorter （ P 〈 0. 05 ）. In the step - through test, compared to sham-operated group, the lantent period in model group was significantly shorter （P 〈 0. 01 ） and the error times were statistically increased（ P 〈 0. 05 ）. Compared with model group, the lantent period in rolipram group were significantly longer （P 〈 0. 05 ）, and the error times were markedly decreased. The assay of the HPLC demonstrated that the activities of PDE4 in hippocampus in model group were higher than those in the sham- operated group and rolipram group. CONCLUSION： Rolipram reduces the activity of PDE4 in hippocampus and enhances the ability of learning and memory after the injury in- duced by ischemia-reperfusion.

关 键 词：咯利普兰 再灌注损伤 CAMP 学习 记忆 

分 类 号：R364[医药卫生—病理学]