慢性低灌注对大鼠基底前脑胆碱能系统及认知功能的影响

The influence of chronic hypoperfusion on the basal forebrain cholinergic system and cognitive function of rats

目的探讨慢性低灌注状态对大鼠基底前脑胆碱能神经系统及认知功能的影响。方法永久结扎SD系大鼠双侧颈总动脉建立大鼠前脑慢性低灌注状态模型,于1、2及4个月时观察基底前脑组织病理学变化、应用免疫组织化学方法检测基底前脑胆碱乙酰转移酶(Cholineacetyltransferase,ChAT)的表达水平、应用改良的MG-2型“Y”型迷宫检测大鼠学习和记忆能力。结果与对照组相比,术后第1、2和4个月时,基底前脑神经元和胶质细胞结构紊乱、呈片状和灶性坏死,ChAT阳性神经元及纤维显著减少(P<0.01),并随时间延长逐渐加重;大鼠全天总反应时间(Totalreactiontime,TRT)明显延长(P<0.01);并且以上两者呈显著负相关(r=-0.83、P<0.01)。结论慢性低灌注状态时,大鼠基底前脑发生缺血性病理改变,导致基底前脑胆碱能神经系统损害,从而在整体水平出现学习记忆障碍。低灌注状态时,基底前脑胆碱能神经系统损伤是认知功能障碍形成的重要机制。

Objective To discuss the influence of chronic hypoperfusion on the basal forebrain cholinergic system and cognitive function of rats.Methods The chronic hypopeffusion model rats were made by permanent occlusion of bilateral common carotid arteries. The learning and memory performance of rats were examined using ＂Y＂ type maze task, while the basal forebrain changes in pathology observed by microscope and the level of choline acetyltransferase estimated by immunohistochemistry after permanent occlusion 1,2 and 4 months.Results The learning ability of hypoperfusion group was severely impaired and ChAT positive ceils and fibers decreased significantly comparing with sham-group （P〈0.01）,while there were a severe loss and necrosis of neuron and glial in basal forebrain during the process. Moreover, as time went on,the learning and memory performance remarkably correlated with the density of cholinergic systems of basal forebrain in hyperpeffusion group.Conclusion Cerebral chronic hypoper-fusion induced by permanent occlusion of bilateral common carotid arteries can cause impairment of cholinergic neurons and decline of learning and memory performance of rats.So acetylcholine may play more important role in the process of cognitive impairment. The further pathogenesis remains to be studied.