Objective To investigate the effectiveness of compound Chai Jin Jie Yu Tablets(CJJYT)in ameliorating cognitive impairment associated with depression and its potential mechanism of action.Methods In vitro experiments,t...Objective To investigate the effectiveness of compound Chai Jin Jie Yu Tablets(CJJYT)in ameliorating cognitive impairment associated with depression and its potential mechanism of action.Methods In vitro experiments,the hippocampus was isolated from the whole brain of the fetal rat and cultured into hippocampal neuron cells.50μM corticosterone(CORT)was added to each group 18 h before the experiment for modeling depression,with the exception of the control group.After modeling,the blank serum group was added with 10%blank serum,the CJJYT group and the venlafaxine group were added with the corresponding 10%drug-containing serum,and the control group and the model group were added with equal volumes of culture medium.The intracellular Ca^2+mean fluorescence intensity,miniature excitatory postsynaptic current(mEPSC)current amplitude,and frequency of different hippocampal neurons were evaluated as indicators of synaptic function in the hippocampal neurons.In addition,the expression of synaptic plasticity related proteins,synaptophysin-α(SYN-α),N-methyl-D-aspartate receptor 2A(NR2A),N-methyl-Daspartate receptor 2B(NR2B),post synaptic density 95 protein(PSD-95),calcium/calmodulin dependent protein kinaseⅡ(CaMKⅡ)and synaptic associated protein(SynGAP)were detected in the hippocampal neurons by immunofluorescence staining and high content analysis(HCA)system.Then,reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the mRNA expression levels of SYN-α,NR2A,NR2B,PSD-95,CaMKⅡand SynGAP.For in vivo experiments,except for those in the blank control group,all rats were treated within a single cage for chronic unpredictable stress-induced depression modeling and subjected to corresponding drug interventions.Behavioral tests were used to detect depressive behavior and determine learning,memory and other cognitive abilities,whereas enzyme-linked immunosorbent assay(ELISA)was used to detect the CORT levels.Golgi-Cox staining was used to observe changes in the synaptic morphology of parahippocampal gyrus CA1 area(CA1)and dentategyrus(DG).Results In vitro,CJJYT treatment reduced the intracellular Ca^2+mean flurorescence intensity in the hippocampal neurons(P<0.05),causing a reduction in the frequency and current amplitude of mEPSC(P<0.05),and thus inhibited the excessive activation of post-synaptic receptors.CJJYT treatment reduced the protein and mRNA expression of SYN-α,NR2A,NR2B and PSD-95 in the hippocampal neurons(P<0.05),increased the mRNA and protein expression of CaMKⅡand SynGAP(P<0.05),and thereby improved the synaptic plasticity of the hippocampal neurons.In vivo,CJJYT intervention improved sucrose preference,voluntary activity,learning and memory ability of Morris water maze test,and suppressed appetite(P<0.05),and increased the despair feeling of forced swimming test(P<0.05).The CORT level was reduced(P<0.05),leading to the repair of synaptic damage in the hippocampal neurons.Conclusions CJJYT can improve the synaptic function of hippocampal neurons and has obvious protective effects on neurons.It can repair the structural damage in the hippocampal neurons,improving the cognitive ability of the depressed model rats.The mechanism of CJJYT improving cognition in depressed rats may be related to the transmission and function of SYN-α/NR and its downstream neurotransmitters.展开更多
针对我国首次采用静止无功补偿器(Static Var Compensator,SVC)抑制次同步振荡(Sub-Synchronous Oscillation,SSO)的工程,分析了该工程中SVC的接入位置、触发方式和控制策略等。基于实时数字仿真(Rea Time Digital Simulator,RTDS),搭...针对我国首次采用静止无功补偿器(Static Var Compensator,SVC)抑制次同步振荡(Sub-Synchronous Oscillation,SSO)的工程,分析了该工程中SVC的接入位置、触发方式和控制策略等。基于实时数字仿真(Rea Time Digital Simulator,RTDS),搭建了针对该工程中SVC控制器进行闭环控制测试的平台。阐述了该平台的框架结构、硬件配置,分析了建模过程中存在的问题,提出了大型系统的建模方法。基于该平台,在典型运行方式和故障方式下,对SVC抑制SSO的效果进行了全面的验证,并仿真分析了SVC抑制SSO时其对交流系统所可能产生的影响。结果表明,所采用的SVC能够抑制SSO现象,并且对系统的暂态稳定性几乎没有影响。展开更多
基金funding support from the National Major New Drug Development Project(No.2017ZX09309026)Provincial Department of Graduate Research Innovation Project of Hunan(No.CX20190565)。
文摘Objective To investigate the effectiveness of compound Chai Jin Jie Yu Tablets(CJJYT)in ameliorating cognitive impairment associated with depression and its potential mechanism of action.Methods In vitro experiments,the hippocampus was isolated from the whole brain of the fetal rat and cultured into hippocampal neuron cells.50μM corticosterone(CORT)was added to each group 18 h before the experiment for modeling depression,with the exception of the control group.After modeling,the blank serum group was added with 10%blank serum,the CJJYT group and the venlafaxine group were added with the corresponding 10%drug-containing serum,and the control group and the model group were added with equal volumes of culture medium.The intracellular Ca^2+mean fluorescence intensity,miniature excitatory postsynaptic current(mEPSC)current amplitude,and frequency of different hippocampal neurons were evaluated as indicators of synaptic function in the hippocampal neurons.In addition,the expression of synaptic plasticity related proteins,synaptophysin-α(SYN-α),N-methyl-D-aspartate receptor 2A(NR2A),N-methyl-Daspartate receptor 2B(NR2B),post synaptic density 95 protein(PSD-95),calcium/calmodulin dependent protein kinaseⅡ(CaMKⅡ)and synaptic associated protein(SynGAP)were detected in the hippocampal neurons by immunofluorescence staining and high content analysis(HCA)system.Then,reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the mRNA expression levels of SYN-α,NR2A,NR2B,PSD-95,CaMKⅡand SynGAP.For in vivo experiments,except for those in the blank control group,all rats were treated within a single cage for chronic unpredictable stress-induced depression modeling and subjected to corresponding drug interventions.Behavioral tests were used to detect depressive behavior and determine learning,memory and other cognitive abilities,whereas enzyme-linked immunosorbent assay(ELISA)was used to detect the CORT levels.Golgi-Cox staining was used to observe changes in the synaptic morphology of parahippocampal gyrus CA1 area(CA1)and dentategyrus(DG).Results In vitro,CJJYT treatment reduced the intracellular Ca^2+mean flurorescence intensity in the hippocampal neurons(P<0.05),causing a reduction in the frequency and current amplitude of mEPSC(P<0.05),and thus inhibited the excessive activation of post-synaptic receptors.CJJYT treatment reduced the protein and mRNA expression of SYN-α,NR2A,NR2B and PSD-95 in the hippocampal neurons(P<0.05),increased the mRNA and protein expression of CaMKⅡand SynGAP(P<0.05),and thereby improved the synaptic plasticity of the hippocampal neurons.In vivo,CJJYT intervention improved sucrose preference,voluntary activity,learning and memory ability of Morris water maze test,and suppressed appetite(P<0.05),and increased the despair feeling of forced swimming test(P<0.05).The CORT level was reduced(P<0.05),leading to the repair of synaptic damage in the hippocampal neurons.Conclusions CJJYT can improve the synaptic function of hippocampal neurons and has obvious protective effects on neurons.It can repair the structural damage in the hippocampal neurons,improving the cognitive ability of the depressed model rats.The mechanism of CJJYT improving cognition in depressed rats may be related to the transmission and function of SYN-α/NR and its downstream neurotransmitters.
文摘针对我国首次采用静止无功补偿器(Static Var Compensator,SVC)抑制次同步振荡(Sub-Synchronous Oscillation,SSO)的工程,分析了该工程中SVC的接入位置、触发方式和控制策略等。基于实时数字仿真(Rea Time Digital Simulator,RTDS),搭建了针对该工程中SVC控制器进行闭环控制测试的平台。阐述了该平台的框架结构、硬件配置,分析了建模过程中存在的问题,提出了大型系统的建模方法。基于该平台,在典型运行方式和故障方式下,对SVC抑制SSO的效果进行了全面的验证,并仿真分析了SVC抑制SSO时其对交流系统所可能产生的影响。结果表明,所采用的SVC能够抑制SSO现象,并且对系统的暂态稳定性几乎没有影响。
