摘要
目的:研究淫羊藿苷(ICA)对精神分裂症模型大鼠认知功能的改善作用及机制。方法:将SD大鼠分为空白对照组、模型组和ICA低、中、高剂量组(15、30、60 mg/kg),除空白对照组外,其余组大鼠均腹腔注射N-甲基-D-天冬氨酸受体拮抗剂MK-801(0.2 mg/kg)复制精神分裂症模型,每天1次,连续14天。造模成功后,ICA各剂量组大鼠灌胃相应药物,空白对照组和模型组灌胃等体积水,每天1次,连续28天。采用Morris水迷宫实验、旷场实验、强迫游泳实验和Y迷宫实验观察大鼠行为学变化;采用Nissl法染色观察大鼠海马组织病理变化;采用酶联免疫吸附法(ELISA)检测大鼠脑组织中胆碱能相关指标[乙酰胆碱(Ach)、胆碱乙酰转移酶(ChAT)、乙酰胆碱酯酶(AchE)]的水平;采用实时荧光定量聚合酶链式反应(PCR)法检测大鼠脑组织中脑源性神经营养因子(BDNF)、细胞外信号调节蛋白激酶(ERK)、环磷腺苷反应元件结合蛋白(CREB)的mRNA的表达水平;采用Western blot法检测大鼠脑组织中BDNF、ERK、CREB蛋白和凋亡相关蛋白[B淋巴细胞瘤2(Bcl-2)及其相关X蛋白(Bax)、胱天蛋白酶3(Caspase-3)]的表达或磷酸化水平。结果:与空白组比较,模型组大鼠逃避潜伏期、T1~T3时段活动路程长度、累积不动时间和脑组织中Caspase-3蛋白的表达水平均显著增加或升高(P<0.05);穿台次数、交替率、海马组织中Nissl染色阳性神经元数以及脑组织中Ach和ChAT水平、Bcl-2/Bax比值、BDNF m RNA和蛋白的表达水平、ERK和CREB mRNA的表达水平、ERK1/2和CREB磷酸化水平均显著减少或降低(P<0.05)。与模型组比较,ICA高剂量组大鼠逃避潜伏期、T1~T3段活动路程长度、累积不动时间、Nissl染色阳性神经元数、脑组织中AchE水平和Caspase-3蛋白的相对表达量均显著减少或降低(P<0.05);穿台次数、交替率,脑组织中Ach和ChAT水平、Bcl-2/Bax比值、BDNF m RNA和蛋白的表达水平、ERK和CREB mRNA的表达�
OBJECTIVE:To study the improvement effects of icariin(ICA)on cognitive function in schizophrenia model rats and its mechanism.METHODS:SD rats were divided into blank control group,model group,ICA low-dose,medium-dose and high-dose groups(15,30,60 mg/kg).Except for blank control group,other groups were given N-methyl-D-aspartate receptor antagonist MK-801(0.2 mg/kg)intraperitoneally to induce schizophrenia rats models,once a day,for consecutive 14 days.After modeling,ICA groups were intragastrically administered with the corresponding drugs,while blank control group and model group were intragastrically administered with the same volume of water,once a day,for consecutive 7 days.The behavioral changes of rats were detected by Morris water maze test,open field test,forced swimming test and Y maze test;the pathological changes of hippocampus were observed by Nissl staining;the levels of cholinergic indexes[acetylcholine(Ach),choline acetyltransferase(ChAT)and acetylcholinesterase(AchE)]in cerebral tissues were detected by ELISA.The expression of BDNF,ERK and CREB mRNA in cerebral tissue were detected by RT-PCR;expression or phosphorylation level of BDNF,ERK,CREB protein,apoptosis related proteins(Bcl-2,Bax and Caspase-3)were detected by Western blot.RESULTS:Compared with blank control group,escape latency,distance at T1-T3,cumulative immobility time and the expression of Caspase-3 protein in cerebral tissues were significantly increased in model group(P<0.05);the times of crossing platform,alternation rate,the number of Nissl staining positive neurons in hippocampus tissues,the levels of Ach and ChAT in cerebral tissues,Bcl-2/Bax ratio,mRNA and protein expression of BDNF,mRNA expression of ERK and CREB,the phosphorylation of ERK1/2 and CREB were significantly decreased(P<0.05).Compared with model group,escape latency,distance at T1-T3,cumulative immobility time,the number of Nissl staining positive neurons,AchE level in cerebral tissues and relative expression of Caspase-3 protein were significantly decreased in ICA
作者
刘运琴
刘燕芹
戢汉斌
肖文昊
林丽
LIU Yunqin;LIU Yanqin;JI Hanbin;XIAO Wenhao;LIN Li(Dept.of Psychiatry,Wuhan Wudong Hospital/Wuhan Second Mental Hospital,Wuhan 430084,China;Operating Room,Wuhan Wudong Hospital/Wuhan Second Mental Hospital,Wuhan 430084,China;Party Secretary Office,Wuhan Wudong Hospital/Wuhan Second Mental Hospital,Wuhan 430084,China;Dept.of Geriatric Psychiatry,Wuhan Wudong Hospital/Wuhan Second Mental Hospital,Wuhan 430084,China;Laboratory of Molecular Cell Biology,School of Basic Medicine,Hubei University of TCM,Wuhan 430065,China)
出处
《中国药房》
CAS
北大核心
2021年第7期812-818,共7页
China Pharmacy
基金
中国博士后科学基金第59批面上资助项目(No.2016M592319)
湖北省卫生健康委2019-2020年度青年人才项目(No.WJ2019Q211)。
