漆黄素对精神分裂症模型大鼠认知功能损伤的影响  

Effects of Fisetin on Cognitive Impairment in Schizophrenia Model Rats

作　　者：兰金滢 吴国江 邹晓伟 万爱兰[1] LAN Jin-ying;WU Guo-jiang;ZOU Xiao-wei;WAN Ai-lan(Department of Psychosomatic Medicine,The First Affiliated Hospital,Nanchang 330006,China;Department of Psychology,School of Public Policy and Administration,Nanchang University,Nanchang 330031,China)

机构地区：[1]南昌大学第一附属医院心身医学科,南昌330006 [2]南昌大学公共政策与管理学院,南昌330031

出　　处：《南昌大学学报（医学版）》2024年第2期18-22,共5页Journal of Nanchang University：Medical Sciences

基　　金：江西省卫健委科技计划项目(20203184)。

摘　　要：目的探究漆黄素(Fisetin)对地卓西平马来酸盐(MK-801)诱导的精神分裂症模型大鼠认知功能损伤的影响。方法将24只SD大鼠随机分为3组:精神分裂症模型组(SZ组)、漆黄素干预组(Fisetin组)、空白对照组(Control组),每组8只,并利用MK-801处理SZ组和Fisetin组,建立精神分裂症模型。建模完成后,对Fisetin组大鼠腹腔注射漆黄素(20 mg·kg^(-1)·d^(-1)),SZ组和Control组大鼠腹腔注射等体积二甲亚砜,连续14 d。利用Morris水迷宫实验对大鼠的学习、记忆功能进行评估;Western-blot检测大鼠海马区钙/钙调素依赖激酶Ⅱ(CaMKⅡ)、细胞外信号调节蛋白激酶(ERK1/2)、环磷酸腺苷反应元件结合蛋白(CREB)的表达及磷酸化水平。结果Morris水迷宫实验结果显示,相较于Control组,SZ组的逃避潜伏期显著延长(P<0.05),空间探索时间显著缩短(P<0.01),穿越原安全平台所在位置次数显著减少(P<0.01);相较于SZ组,Fisetin组逃避潜伏期显著缩短(P<0.05),空间探索时间显著延长(P<0.05),穿越原安全平台所在位置次数显著增加(P<0.05)。蛋白表达方面,3组大鼠海马组织中CaMKⅡ、ERK1/2、CREB的表达水平比较差异无统计学意义(P>0.05);与Control组相比,SZ组CaMKⅡ、ERK1/2、CREB的磷酸化水平显著降低(P<0.05或P<0.01);与SZ组相比,Fisetin组CaMKⅡ、ERK1/2、CREB的磷酸化水平显著升高(P<0.01)。结论漆黄素可缓解MK-801诱导的精神分裂症模型大鼠的认知功能损伤,其机制可能与提高CaMKⅡ、ERK1/2、CREB的磷酸化水平有关。Objective To investigate the effects of Fisetin on cognition impairment in schizophrenia model rats induced by dizocilpine(MK-801).Methods 24 Sprague Dawley(SD)rats were randomly divided into three groups(n=8):schizophrenia group(Group SZ),Fisetin group(Group Fisetin)and control group(Group C).Group SZ and Group Fisetin were induced by MK-801 to establish the schizophrenia models.After modeling was completed,Group Fisetin was treated with Fisetin(20 mg·kg^(-1)·d^(-1))by intraperitoneal injection,and Group SZ and Group C were injected intraperitoneally with an equal volume of Dimethyl sulfoxide for 14 consecutive days.Learning and memory functions of rats were evaluated with the Morris water maze assay;the protein expression and phosphorylation levels of calcium/calmodulin-dependent protein kinaseⅡ(CaMKⅡ),extracellular regulated protein kinase(ERK1/2)and cAMP-response element binding protein(CREB)were detected in hippocampus of rats by Western-blot.Results The results of Morris water maze showed that compared with Group C,the escape latency of Group SZ was significantly increased(P<0.05),the space exploration time was significantly decreased(P<0.01),and the times of traversing the location of the original safety platform was significantly reduced(P<0.01).Compared with Group SZ,the escape latency of Group Fisetin was significantly decreased(P<0.05),the space exploration time was significantly increased(P<0.05),and the times of traversing the location of original safety platform was significantly increased(P<0.05).In terms of protein expression,there were no significant differences in the expression levels of CaMKⅡ,ERK1/2 and CREB in hippocampal tissues of the three groups of rats(P>0.05).The phosphorylation levels of CaMKⅡ,ERK1/2,and CREB in Group SZ were significantly lower compared with those of Group Control(P<0.05 or P<0.01);and compared with those of Group SZ,the phosphorylation levels of CaMKⅡ,ERK1/2,and CREB were significantly higher in Group Fisetin(P<0.01).Conclusion Fisetin can alleviate MK-80

关 键 词：漆黄素 MK-801 精神分裂症 认知功能损伤 动物 实验 大鼠 

分 类 号：R285.5[医药卫生—中药学]