吡拉西坦对大鼠慢性脑缺血所致认知功能障碍和神经元损伤的保护作用  

Protective effects of piracetam against cognitive deficits and neuronal degeneration induced by chronic cerebral ischemia in rats

作　　者：廖赟[1] 李玲[1] 刘学源[2] 

机构地区：[1]上海市第十人民医院药剂科,上海200072 [2]上海市第十人民医院神经内科,上海200072

出　　处：《药学服务与研究》2007年第1期32-36,共5页Pharmaceutical Care and Research

基　　金：上海市自然科学基金重点资助项目(No.044119634)

摘　　要：目的:观察吡拉西坦(别名脑复康)对慢性脑部低灌注所致认知功能障碍和神经元损伤的改善作用。方法:采用大鼠双侧颈总动脉永久性结扎模型,30只SD大鼠分为假手术组、脑缺血组和吡拉西坦治疗组,每组10只。吡拉西坦治疗组用吡拉西坦600 mg/kg灌胃,1次/d,从手术当天开始,持续37 d。Morris水迷宫实验用于检测空间学习记忆行为。生化测量脑内花生四烯酸代谢产物血栓素B2(TXB2)和6-酮前列腺素F1α(6-酮-PGF1α)的水平。HE染色观察大脑皮层和海马神经元的组织形态学改变,免疫组化分析p53蛋白及Bax蛋白的表达。结果:慢性脑部低灌注能够引起大鼠学习记忆损伤,表现为逃离潜伏期的延长和在目标象限中游泳时间的缩短,伴随着TXB2和6-酮-PGF1α水平的升高,p53和Bax蛋白的高表达以及皮层和海马神经元延迟性损害。吡拉西坦灌胃可显著提高损伤大鼠的学习记忆能力,降低TXB2水平,抑制p53和Bax蛋白的过量表达,改善神经元结构异常。结论:吡拉西坦对大鼠慢性脑缺血有保护作用,提示其可能在血管性痴呆的治疗中发挥积极有效的作用。Objective： To study the protective effects of piracetam against cognitive deficits and neuronal degeneration induced by chronic cerebral hypoperfusion in rats. Methods： Chronic hypoperfusion was induced by permanent ligation of bilateral common carotid arteries of rats. Thirty SD rats were randomly divided into 3 groups （n= 10） including sham-operated group, cerebral ischemia group and piracetam-treated group. In piracetam-treated group, piracetam （600 mg/kg） was administered by gastrogavage for 37 d. Morris water maze was used to measure spatial learning and memory ability of the rats. The levels of TXB2 and 6-keto-PGF1a were determined by biochemistry method. Morphological changes of neurons in cortex and hippocampus were examined by HE staining. The expression of p53 and Bax proteins was assayed by immunohistochemical method. Results： Chronic cerebral hypoperfusion resulted in memory impairment of rats shown by prolonged escape latency and shortened time for swimming in the target quadrant. The levels of TXB2 and 6-keto-PGF1a were increased. Bax and p53 proteins were overex- pressed and neurons in cortex and hippocampus were damaged. Administration of piracetam markedly improved the memory impairments, reduced the levels of metabolites of arachidonic acid to their normal levels, and attenuated neuronal damage. Conclusion： The ability of piracetam to attenuate memory deficits and neuronal damage after ischemia may be beneficial to the treatment of cerebrovascular dementia.

关 键 词：吡拉西坦 脑缺血 认知障碍 神经元 大鼠 

分 类 号：R964[医药卫生—药理学]