| We have a widely knowledge that the disease location of mental health the brain and also have a closely relationship with phlegm and stagnation.The main pathological mechanism is phlegm and stagnation interfere with each other then destroy the function of the brain.So the study was based on mental health theory of traditional Chinese medicine(TCM)and we developed a innovative formulas-Yu-Dian-Tang for cognitive dysfunction mice model of schizophrenia,and observed the effect on CREB-BDNF signaling pathway in order to infer the underlying therapeutic mechanism of Yu-Dian-Tang for cognitive dysfunction of schizophrenia.Objective:to prove Yu-Dian-Tang was a effective and safely intervention for cognitive dysfunction mice model of schizophrenia.And at the same time,based on the network pharmacology theory to clarify the underlying thera-peutic mechanism of Yu-Dian-Tang for cognitive dysfunction of schizo-phrenia.Part 1Methods:Divided the adult male SD rats into the blank group,the model group,the control group,and the observation group.Manufacturing the mice model using MK-801,which is the non-competitive receptor blocker of NMDA.The interventions were Risperdone or Yu-Dian-Tang,and the outcome was behavioral observation tested by MORRIS water maze equipment:(1)Observing the changes of escape latency in the different points-in-time to evaluate the capacities of spatial discrimination and learning-memory of mice model.(2)Observing the frequency of through the security platform,and the ratio of activity trajectory and time to evaluate the capacities of space exploration of mice model.Results:(1)The results of escape latency in observing group were shorter than model group and control group in the points-in-time of 4-day,and 5-day after the learning(p<0.05).(2)The results of the observing group was better than model group in the frequency of through the security platform(p<0.05).In the ratio of activity trajectory and time that the observing group was better than model group and control group(p<0.05).Conclusion:(1)Yu-Dian-Tang could improve the capacities of spatial discrimin-ation and learning-memory of mice model.(2)Yu-Dian-Tang could improve the capacities of the capacities of space exploration of mice model.Part 2Methods:Divided the adult male SD rats into the blank group,the model group,the control group,and the observation group.Manufacturing the mice model using MK-801,which is the non-competitive receptor blocker of NMDA.The interventions were Risperdone or Yu-Dian-Tang,and the outcome were the expression of CREB protein,BDNF protein and the BCL-2 protein,and also the phosphorylation of CREB protein tested by West Bold method.Results:(1)The expressions of CREB protein in observing group were better than model group at the points-in-time of 7-day,14-day,and 28-day after intragastric infusion(p<0.05).(2)Results of the phosphorylation of CREB protein in observing group and control group were better than model group and blank group at the points-in-time of 7-day,14-day,and 28-day after intragastric infusion(p<0.05).And the observing group was better than control group(p<0.05).(3)The expressions of BDNF protein in hippocampus in observing group and control group were better than model group and blank group at the points-in-time of 7-day,14-day,and the observing group was better than control group(p<0.05).At 28-day,the expressions of BDNF protein in hippocampus in observing group and control group were better than model group and blank group(p<0.05).While there was no significant difference between observing group and control group(p>0.05).(4)The expressions of BCL-2 protein in hippocampus in observing group was better than control group,model group and blank group at the points-in-time of 7-day,14-day,and 28-day after intragastric infusion(p<0.05),and there was no significant difference between control group and blank group(p>0.05),and blank group was better than model group(p<0.05).Conclusion:(1)Yu-Dian-Tang could improve the expressions of CREB protein,BDNF protein,and BCL-2 protein,as well as the phosphorylation of CREB protein.(2)The therapeutic effect of Yu-Dian-Tang for CREB-BDNF signaling pathways was multiple-targets.Part 3Methods:Divided the adult male SD rats into the blank group,the model group,the control group,and the observation group.Manufacturing the mice model using MK-801,which is the non-competitive receptor blocker of NMDA.The interventions were Risperdone or Yu-Dian-Tang.The outcomes were the expressions of the four important node proteins(AKT,Raf,CaMK,and PKA)in CREB-BDNF signaling pathways based on network pharma-cology theory tested by West Bold method.Results:(1)There were no significant difference of the expressions of AKT in blank group,model group and observing group at the points-in-time of 7-day,14-day,and 28-day after intragastric infusion(p>0.05).(2)There were no significant difference of the expressions of Raf in blank group,model group and observing group at the points-in-time of 7-day,14-day,and 28-day after intragastric infusion(p>0.05).(3)The expressions of CaMK in hippocampus in observing group was higher than blank group and model group at the points-in-time of 7-day,14-day,and 28-day after intragastric infusion(p<0.05).(4)The expressions of PKA in hippocampus in observing group was higher than blank group and model group at the points-in-time of 7-day,14-day,and 28-day after intragastric infusion(p<0.05).Conclusion:(1)The regulation of CREB-BDNF signing pathways of Yu-Dian-Tang was activating the CaMK pathway and cAMP pathway.(2)The second and the third experiments,from the level of molecular biology to elucidate the Yu-Dian-Tang for the treatment of cognitive impairment model of schizophrenia " removed phlegm and blood stasis,broken Qi stagnation" in TCM treatment essence provides a preliminary experimental basis.(3)Based on the above three experiments,MK-801 elaborated based on glutamate dysfunction cognitive impairment model of schizophrenia of pathological and physiological basis and verification "phlegm stasis,blood stasis and Qi stagnation" in TCM machine that belong to hippocampal nerve cell damage and neurotransmitter disorder correlation provides a preliminary experimental research foundation. |
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