| Objective:By recording the dynamic changes of related neurotransmitters and behavioral disorder in the process of VCI,investigate the incidence of VCI track,and improve the basic research of VCI.Take Xiongma drip pills intervention to explore the mechanism,seek the time point when Xiongma drip pills have an effect.Methods:Using 2-VO prepared VCI rat model,intravenous infusion needle puncture method cisternal cerebrospinal fluid continuous acquisition,preparation of model 3d,7d,14d,28d,42d,56d collect cerebrospinal fluid of rats,the use of ultra-efficient liquid chromatography-mass spectrometry detection of acetylcholine(Ach)content;high performance liquid associated with electrochemical detection technology norepinephrine(NE),dopamine(DA)content;?-aminobutyrate measured by enzyme-linked immunosorbent assay acid(GABA)content.Preparation Model 28d,42d,Morris water maze learning and memory abilities of rats was measured;Preparation Model 56d,eight-arm radial maze learning and memory abilities of rats were measured;Preparation Model 7d,14d,28d,42d with large mouse social behavior to contact the instrument number,duration of exposure as an indicator to detect changes in rat social behavior;Preparation model 42d,using animal experiments treadmill measured physical activity in rats.3d model began to build before oral administration,orally twice daily gavage 60d,dynamic observation of effects of drugs on the indicators.Results:(1)The ability of learning and memory measurement results:?Morris Water Maze Results:Compared with sham group,the preparation of model 28d learning and memory in rats no significant change(P>0.05);preparation of model 42d,escape latency was significantly increased(P<0.01),the number of rats crossing platform significantly reduced(P<0.01);compared with the model group,Xiongma drip pills high and low dose group were significantly reduced escape latency(P<0.01);? eight-arm maze results:Preparation of model 56d,foraging time model group increased significantly(P<0.05).(2)Determination of social behavior in Rats Results:Compared with sham group,the first model in the 28d,the model number of the contact group of rats was no significant difference(P>0.05),but the duration of exposure but there was significant reduction(P<0.05),the first model in the 42d,the number of contact model rats,duration of exposure significantly reduced(P<0.01,P<0.05)appears.Compared with model group,casting the first 28d,the number of contacts Xiongma drip pills high dose group were significantly increased(P<0.05),Xiongma drip pills high and low dose group duration of exposure was significantly increased(P<0.05,P<0.01);modeling section 42d,the number of Xiongma drip pills rats exposed to low-dose and duration of exposure increased(P<0.05);modeling section 42d,physical activity of rats in each group compared to no significant difference(P>0.05).(3)Nerve transmitter measurement results:Compared with sham group,the neurotransmitter content in cerebrospinal fluid of rats in model group neural follows:? Ach in modeling 7d decreased significantly(P<0.05);? NE showed no significant change(P>0.05);? DA content modeling 28d,56d decreased significantly(P<0.05);? GABA in modeling 28d was significantly higher(P<0.05).Compared with model group,drug group neurotransmitter content changes are as follows:first modeling 42d,56d,the content of DA rat cerebrospinal fluid Xiongma drip pills low dose group was significantly higher(P<0.05);compared with the model group,modeling section 7d,28d,cerebrospinal fluid Xiongma drip pills low dose group was significantly decreased GABA(P<0.01,P<0.05).(4)Correlation analysis:In the modeling section 28d,social capacity showed a positive correlation(P<0.05)and the DA was with GABA was negatively correlated(P<0.05);in the modeling section 56d,learning and memory exhibits the DA It was negatively correlated(P<0.05).Conclusion:(1)Using 2-VO method can be successfully established rat model of VCI.Behavioral studies have shown that social behavior disorder prior to learning and memory impairment,since the model first 28d start,VCI rats first appeared in social behavior disorders,as time increases,social barriers gradually increased learning and memory disorders accompanied by Article 42d,continued to 56d.(2)VCI rats in the pathogenesis of the neurotransmitter associated with changes in preparation 7d model,Ach decreased mainly;preparation of model 28d,to DA content decreased,GABA levels increased mainly;Preparation Model 56d to DA decreased mainly.Should be modeling the first 7d,giving Ach receptor agonist;in the preparation of model 28d,given amino acid receptor antagonists;in the preparation of model 28-56d,given DA receptor agonist.(3)VCI histological changes in rat behavior pathogenesis and neurotransmitters have some relevance.Social capacity VCI rats obstacles stages,namely the first 28d,social behavior and DA was positively correlated with GABA was negatively correlated with the intensi:fication of injury,correlation disappears,and the body's self-regulation may be related,but severe memory impairment in learning stage,namely 56d,learning and memory was negatively correlated with the DA.(4)Xiongma drip pills on VCI pathogenesis of rat behavior and neurotransmitter changes in cerebrospinal fluid has a certain intervention.Preparation Model 28d-42d,the ability to continue to improve social behavior in the modeling section 42d,the drug group learning and memory performance improved significantly,and Xiongma drip pills low dose(0.75g crude drug · kg-1)effect is more significant.Low doses of Xiongma drip pills in preparation model 7d,28d,a significant reduction in CSF GABA in rats,in the preparation of model 42d,56d,significantly increased cerebrospinal fluid in DA content. |
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