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淫羊藿苷对精神分裂症模型大鼠认知功能的改善作用及机制
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篇名: 淫羊藿苷对精神分裂症模型大鼠认知功能的改善作用及机制
TITLE: Study on Improvement Effects of Icariin on Cognitive Function in Schizophrenia Model Rats and Its Mechanism
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、60mg/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(0.2mg/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Westernblot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、BDNFmRNA和蛋白的表达水平、ERK和CREBmRNA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、BDNFmRNA和蛋白的表达水平、ERK和CREBmRNA的表达水平、ERK1/2和CREB的磷酸化水平均显著增加或升高(P<0.05)。ICA低、中剂量组大鼠上述部分指标较模型组显著改善(P<0.05)。结论:ICA可改善精神分裂症模型大鼠的认知功能,其作用机制可能与调节胆碱能系统、抑制神经元凋亡、促进BDNF/ERK/CREB信号通路的表达有关。
ABSTRACT: OBJECTIVE:To study the improvement effects of ica riin(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 com changes of rats were detected by Morris water maze test ,open field test , forced swimming test and Y maze test 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 T 1-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 ERK 1/2 and CREB were significantly decreased (P<0.05).Compared with model group , escape latency ,distance at T 1-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 high-dose group (P<0.05);the times of crossing platform ,alternation rate ,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 ERK 1/2 and CREB were increased significantly(P<0.05). Above indexes in ICA low-dose and medium-dose groups were partially improved significantly than model group(P<0.05). CONCLUSIONS :ICA can improve cognitive function in schizophrenia model rats.Its mechanism may be related to regulating cholinergic system ,inhibiting neuronal apoptosis ,and promoting the expression of BDNF/ERK/CREB signaling pathway.
期刊: 2021年第32卷第07期
编辑: 刘运琴,刘燕芹,戢汉斌,肖文昊,林丽
AUTHORS: LIU Yunqin ,LIU Yanqin ,JI Hanbin ,XIAO Wenhao ,LIN Li
关键字: 淫羊藿苷;精神分裂症;认知功能;BDNF/ERK/CREB信号通路;神经元凋亡;胆碱能系统;大鼠
KEYWORDS: Icariin; Schizophrenia; Cognitive function ; BDNF/ERK/CREB signaling pathway ; Neuronal apoptosis ;
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