咯利普兰对全脑缺血-再灌注损伤大鼠的影响

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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。 Objective To observe the effects of rolipram on the pathological changes, learning and memory abilities, and the activity of phosphodiesterase 4 (PDE4) in hippocampus of rats with global brain ischemia-reperfusion injury. Methods The rat model of global cerebral ischemia was established by four-vessel occlusion. The rats were randomly divided into sham operation group, model group, rolipram 1 mg · kg-1 treatment group and rolipram 0.3 mg · kg-1 treatment group , 6h after intraperitoneal injection for the first time. The water maze and inhibition avoidance test were used to test the learning and memory of the rats. After 2 weeks, the rats were sacrificed by perfusion fixation and Nissl staining was performed to observe the histopathology of the brain tissue. The brain homogenates were prepared for detection of rats by high performance liquid chromatography Hippocampal PDE4 activity. Results After global cerebral ischemia-reperfusion injury in rats, the pathological changes of brain tissue were obvious. Compared with the control group, the learning and memory abilities were significantly decreased and the PDE activity was significantly increased. Rolipram after treatment to improve ischemia-reperfusion injury-induced changes in brain tissue pathology, compared with the model group significantly enhanced learning and memory ability, PDE activity was significantly reduced. And rolipram 0.3mg · kg-1 treatment group effect is significant. Conclusion Rolipram can reduce the PDE activity of hippocampus in rats with global cerebral ischemia-reperfusion injury and improve learning and memory dysfunction and pathological changes of brain after global cerebral ischemia-reperfusion in rats.
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