咯利普兰对全脑缺血-再灌注损伤大鼠的影响

 目的观察咯利普兰对全脑缺血-再灌注损伤大鼠脑组织病理学改变、学习记忆能力及海马磷酸二酯酶4(PDE4)活性的影响。方法采用大鼠四血管阻断法制备全脑缺血模型,将大鼠随机分成假手术组、模型组、咯利普兰1mg·kg^-1治疗组及咯利普兰0.3mg·kg^-1治疗组,术后6h腹腔注射首次给药。通过水迷宫和抑制回避实验测试其学习记忆水平,2周后将大鼠处死灌注固定后行尼氏染色进行脑组织病理形态学观察,并制备脑组织匀浆应用高效液相色谱法检测大鼠海马组织PDE4活性。结果大鼠全脑缺血-再灌注损伤后,脑组织病理学改变明显,较对照组学习记忆能力显著降低,PDE活性显著升高。咯利普兰治疗后改善缺血再灌注损伤所致的脑组织病理学改变,较模型组学习记忆能力显著增强,PDE活性显著降低。且以咯利普兰0.3mg·kg^-1治疗组效果显著。结论咯利普兰能降低全脑缺血-再灌注损伤大鼠海马PDE活性,并改善全脑缺血-再灌注大鼠的学习记忆功能障碍及脑组织病理学改变。

Effects of Rolipram on Global Cerebral Injury Induced by Ischemia-Reperfusion

OBJECTIVE To investigate the effect of rolipram on histopathology,memory function and PDE activity following global cerebral injury induced by ischemia-reperfusion(I-R) in rats.METHODS The global cerebral ischemia-reperfusion injury model was made by four-vessel occlusion in rats.The rats were randomly divided into sham-operated group,I-R group,rolipram 0.3 mg·kg^-1group and rolipram 1 mg·kg^-1group.Rolipram was administered once a day after the operation for 2 weeks.The learning and memory abilities were measured by Morris water maze and step-though training.After behavioral test was completed,the brain were immediately removed for nissl(toluidine blue) staining and the PDE activity of the hippocampus were evaluated by HPLC.RESULTS In the Morris water maze test,compared with sham-operated group,the escape lantency of the I-R group were significantly longer;compared with the model group,the escape lantency of the 0.3 mg·kg^-1 or 1 mg·kg^-1 rolipram group were significantly shorter;in the step-through test,compared with sham-operated group,the lantency of the I-R group were significantly shorter and the error times were increased statistically significant,compared with the model group,the lantency of the 0.3 or 1 mg·kg^-1 rolipram group were significantly longer,and the error times were decreased statistically significant.Histological examination of brains from sham operated animals revealed no cell damage at all.Application of 0.3 or 1 mg·kg^-1 rolipram resulted in a reduction of neuronal cell loss in the hippocampal CA1 sector.The HPLC assay demonstrated that the activities of PDE in hippocampus of model group were higher than those in the sham-operated group and rolipram group.CONCLUSION Rolipram could reduce the activity of PDE4,neuronal damage in hippocampus,and enhance the ability of learning and memory after the injury induced by ischemia-reperfusion.