氟西汀对慢性脑缺血大鼠工作记忆损伤的保护作用及其机制的研究  

Effect and mechanism of fluoxetine on improving working memory in rats with chronic cerebral ischemia

作　　者：肖敏 张力[1] 赵宏峰 经屏 Xiao Min;Zhang Li;Zhao Hongfeng;Jing Ping(Department of Neurology,the Central Hospital of Wuhan,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430014,China)

机构地区：[1]华中科技大学同济医学院附属武汉中心医院神经内科,武汉430014

出　　处：《中国脑血管病杂志》2020年第6期320-326,共7页Chinese Journal of Cerebrovascular Diseases

基　　金：武汉市卫生和计划生育委员会科研项目(WX18D16)。

摘　　要：目的探讨氟西汀对大鼠慢性脑缺血所致工作记忆损伤的改善作用及其作用机制。方法选用Sprague Dawley雄性大鼠44只,采用双侧颈总动脉结扎术建立慢性脑缺血模型,将其分为假手术组(10只)、缺血模型组(12只)、缺血+氟西汀组(12只)、假手术+氟西汀组(10只)。氟西汀在缺血1周后经灌胃给药,持续给药4周。假手术组与缺血模型组给予相同体积的等渗盐水。采用改良的水迷宫实验检测各组大鼠的工作记忆表现,该实验持续4 d;采用免疫印迹法检测各组大鼠前额皮质中神经元标记物神经元核、星形胶质细胞标记物S-100β、G蛋白门控内向整流钾离子(GirK)通道蛋白(GirK1、GirK2、GirK3)以及分拣连接蛋白27(SNX27)的表达水平并进行组间比较。结果(1)4组大鼠游泳速度组间差异无统计学意义(P>0.05)。在训练试验中,4组大鼠逃逸潜伏期及游泳距离的组间差异均无统计学意义(均P>0.05)。在记忆保持试验中,与假手术组同时点比较,缺血模型组大鼠在实验第2、3、4天逃逸潜伏期明显延长[第2天:(48.2±6.3)s比(27.4±4.0)s,第3天:(53.9±6.4)s比(29.4±6.3)s,第4天:(41.4±4.9)s比(23.8±3.7)s;均P<0.05];与缺血模型组同时点比较,缺血+氟西汀组大鼠在实验第3、4天逃逸潜伏期延长得到逆转[分别为(31.0±6.6)、(26.2±3.7)s,均P<0.05]。在记忆保持试验中,与假手术组同时点比较,缺血模型组大鼠在实验第2、3、4天游泳距离明显增加[第2天:(553±76)cm比(313±51)cm,第3天:(619±81)cm比(329±65)cm,第4天:(433±48)cm比(282±47)cm;均P<0.05];与缺血模型组同时点比较,缺血+氟西汀组大鼠在实验第2、3、4天游泳距离的增加得到逆转[分别为(373±54)、(321±70)、(279±44)cm,均P<0.05]。(2)4组大鼠神经元标记物神经元核抗体及星形胶质细胞标记物S-100β的相对灰度值差异均无统计学意义(均P>0.05)。(3)4组大鼠GirK1膜蛋白表达的差异无统计学意义(P>0.05),假手术组�Objective To observe the protective effects of fluoxetine on working memory impairment induced by chronic cerebral ischemia and further explore its mechanism in rats.Methods The rat model of chronic cerebral ischemia was made by surgical ligation of the bilateral carotid artery.44 male Sprague Dawley rats were divided into sham group(n=10),ischemic model group(n=12),ischemic+fluoxetine group(n=12),and sham+fluoxetine group(n=10).Fluoxetine was administered by gavage after 1 week of ischemic surgery and continued for 4 weeks.The sham group and the ischemic model group were given the same volume of 0.9%saline.The performance of working memory was tested by a modified Morris water maze experiment that lasted for 4 days.The expression of neuronal nuclei(NeuN),S-100β,G protein gated inwardly rectifying K channels 1,2,and 3(GirK1,2,and 3),and sorting nexin 27(SNX27)in the prefrontal cortex(PFC)of rats were tested by Western blot,and compare between groups.Results(1)There was no significant difference in swimming speed among the four groups(P>0.05).In the training experiment,there was no significant difference among the four groups in the escape latency and the swimming distance(both P>0.05).In the memory retention test,the escape latency of rats in the ischemic model group was significantly increased on 2nd,3rd and 4th day compared with the sham group(day 2:[48.2±6.3]s vs.[27.4±4.0]s,day 3:[53.9±6.4]s vs.[29.4±6.3]s,day 4:[41.4±4.9]s vs.[23.8±3.7]s;all P<0.05).The escape latency of rats in the ischemia+fluoxetine group on 3rd and 4th day was decreased compared with the ischemia model group([31.0±6.6]s,[26.2±3.7]s,respectively;both P<0.05).In the memory retention test,the swimming distance of rats in the ischemic group was significantly increased on 2nd,3rd and 4th compared with the sham operation group(day 2:[553±76]cm vs.[313±51]cm,day 3:[619±81]cm vs.[329±65]cm,day 4:[433±48]cm vs.[282±47]cm;all P<0.05).The swimming distance in the ischemic+fluoxetine group on 2nd,3rd and 4th day was decreased compared

关 键 词：氟西汀 脑缺血 记忆 短时 G蛋白偶联内向整流钾通道 

分 类 号：R965[医药卫生—药理学]