| Longer lasting performance in cognitively demanding tasks leads to an exhaustion of cognitive resources and to a state commonly described as mentalfatigue or Burnout.Mental fatigue refers to a repeating single task or an intensive work leading to high-intense nervous system,causing activity decreased and negative emotions.In the aspect of cognitive,it shows aprosexia,slowness of thought and deterioration in memory faculties.In the emotional aspects,it shows negative emotions,such as bored,depressed,vexation,complain.It also can trigger variety of physical and mental diseases,such as body hypofunction,insomnia,migraine,urticaria,menstrual disorders.There is no standard concept of mental fatigue up to date,nor is the pathogenesis.Therefore,having collected and sorted TCM theory our research confirm that the principal pathogenesis is liver depression and spleen deficiency.Meanwhile,having collected and sorted domestic and foreign literature,we aims to filter the bestmodelling method to build animal model of mental fatigue.By observing the regulatory function of the prescription of modified Ti Fu Kang on model rat' behavior and excitement-inhibiting balance in CNS,we will highly improve exploring the neurophysiologic mechanism.This may offer further studies and methods for the prevention and treatments of mental fatigue.Part ? Theoretical ResearchTheoretical ? Mental Fatigue in Traditional Chinese MedicineAccording to the analysis of pathogenic factors and clinical features,mental fatigue can be considered as the content of fatigue or weary in TCM.It lays particular stress on the mental symptoms,which is under the category of the theory of seven emotions.The changes such as the decrease of cognitive function and negative emotions caused by continuous single job or intense intellectual work are related with heart,spleen and liver in TCM.Liver stagnation and spleen deficiency,the core pathogenesis,affect each other and therefore aggravate the condition.Thus,mental fatigue should be treated according to spleen and liver.The author put forward the prescription of modified Ti Fu Kang according to the principle of soothing liver to relieve depression and regulating spleen qi.Theoretical ? Literature Research on the Modeling Methods of Mental FatigueAccording to the literature review on the animal model of mental fatigue home and abroad,the author summarized the current modeling methods,including method of electroshock seizure experiment combining method of bounding rats with cylinder,method of bounding rats with cylinder,exhaustive swimming method,method of putting rats in the cage,exhaustive swimming method plus method of putting rats in the cage,treadmill running method and method of standing on small platform station with water environment.Based on statistical results,the method of standing on small platform station with water environment was used more often than others.The method takes advantage of the character that rats are fear of water and affects the cognitive function and changes of negative emotions through sleep deprivation.The method has few effects on skeletal muscles of rats.Therefore,it is similar to the symptoms of mental fatigue to the most.However,it cannot be unified for the modeling object,intensity and equipment and so on in the animal model of mental fatigue with method of standing on small platform station with water environment and therefore further experimental demonstration is needed.Part ? Experiment ResearchExperiment ? Effects of Sleep Deprivation with MMPM on the General Condition and Behavioral Experiment of RatsObjective:To observe effects on behavior of rats with modified multiple platform method(MMPM)for continuous 72h,96h,120h,144h and 168h to select optimum molding intensity of animal model for mental fatigue.Methods:Evaluate behavioral changes of rats with general observation,body weight measurement,elevated plus-maze(EPM),passive avoidance response and grip strength test.Results:Firstly,changes of general signs:The normal group was in good condition,while the model groups showed molt,loose stool,anxiety,high vigilance,irritability and worry,etc,which became worse with the time extension of molding.The death of rats in the model groups started to occur after 144h of molding.After finishing 168h-molding,the death rate of rats in the model groups was 67.7%.There was no sequential research of the model groups.Secondly,body weight changes:With the time extension of molding,body weight of rats in the normal group was increasing while in the model groups decreasing.At the same time points,there was no statistical difference in the body weight among every model group.Thirdly,EPM test:Compare to the normal group,time needed for the entrance of open lazy arm in the 72h,96h and 120h groups was all obviously increasing(p<0.05),while in the 144h group,it increased the most(p<0.01).Time for staying in the center area decreased in every model group.The total number of times for entering into the lazy arm was increasing and the 72h group showed significant increase(p<0.05).Fourthly,passive avoidance response test:Compare to the normal group,the incubation period of rats was obviously shortened in every model group except the 144h group(P<0.01)and their scores of false reaction showed increasing trend.Fifthly,grip strength test:Values of grip strength were reducing in every model group compared with the normal group,and the 96h group showed significant difference(p<0.05)while the 144h group had the most obvious difference(p<0.01).Conclusion:Modeling of sleep deprivation with MMPM can cause the decrease of cognitive function of rats,negative emotion and muscle fatigue.The modeling intensity of 72h indicated the most obvious difference in the risk assessment and decision-making ability of rats.Meanwhile,it showed decreased ability of learning and memory,anxiety and muscle fatigue,which were exactly similar to the symptoms of mental fatigue.Experiment ? Effects of Modified Ti Fu Kang on the General Condition and Cognitive Function of Rats with Mental FatigueObjective:Copy the animal model of mental fatigue.To observe effects of modified Ti Fu Kang on the cognitive ability of rats through behavior assessment.Methods:Copy the animal model of mental fatigue by sleep deprivation with MMPM for 72 hours.Meanwhile,observe changes of general condition,body weight,elevated plus-maze(EPM)and passive avoidance response test after pharmaceutical intervention of rats.Results:Firstly,changes of general signs:The control group was in good condition during the molding.But the model group showed wild hair without luster,decrease of ingestion,increased frequency of standing lean on the wall,behavior of tending to jump out of water tank,rising vigilance,confrontation with each other occasionally and loose stool.There was no significant difference between the model group and the low-dose TCM group.Symptoms in the rest three groups were alleviated.Secondly,body weight changes:With the time extension during the modeling,body weight in the normal group was increasing,while it decreased in the model group and other medical groups.There was no statistical difference between the model group and each medical group.Thirdly,EPM test:Compare to the control group,time needed for entering into the open lazy arm was extending(p<0.01),while the time needed in the western medicine group and the middle-dose TCM group was significantly shortened in the comparison of the model group(p<0.05).In the high-dose TCM group,time for the entrance was most shortened(p<0.01)and the residence time in the center area was increasing at the same time(p<0.05).Fourthly,passive avoidance response test:The incubation period in the model group was shortened compared with the control group(p<0.01).Compare to the model group,the incubation period in the high-dose TCM group extended obviously(p<0.05).There was no statistical difference among each group in the scores of false reaction.Conclusion:It successfully copied the animal model of mental fatigue.Besides,modified Ti Fu Kang can improve the ability of subjective risk assessment,decisionmaking ability and the ability of learning and memory of rats.Experiment ? Effects of Modified Ti Fu Kang on the Amino Acids Transmitter in Corpus Striatum of Model Rats with Mental FatigueObjective:To study the effects of modified Ti Fu Kang on the decrease of cognitive function and the amino acids transmitter in corpus striatum of model rats with mental fatigue and to explore mechanism of drug action.Methods:Extract tissues of corpus striatum of rats in experiment two.Detect content of Glu and GABA adapting high-performance liquid chromatography with electrochemical detection.Results:Compare to the control group,levels of Glu and GABA in corpus striatum in the model group was rising(p<0.01)while they decreased obviously in the western medicine group and high-dose TCM group(p<0.01).Conclusion:Modified Ti Fu Kang can keep the dynamic balance of Glu and GABA levels to improve cognitive ability probably through the regulation of Glu and GABA levels in corpus striatum.Experiment ? Experiment four:Effects of Modified Ti Fu Kang on the Genetic Expression of Relevant Index of GABA Neurons System in Model Rats of Mental Fatigue Objective:To observe effects of mental fatigue on the genetic expression of relevant index of GABA neurons system in corpus striatum of rats and to study the regulation of modified Ti Fu Kang on it.Methods:Observe genetic expression of relevant index of GABA neurons system in corpus striatum of rats in experiment two applying RT-PCR technique.Results:After the modeling of sleep deprivation with MMPM,GABA composition factor GAD67 in corpus striatum of rats,the regulatory molecule of GABA metabolism GAT-1 and GAT-3 showed abnormal changes.Compared to the control group,mRNA transcription levels of GAD67 and GAT-3 in the model groups increased exceedingly(p<0.01)and the GAT-1 level rose obviously(p<0.05).Receptor mRNA transcription level of GABAA?5 reduced extremely(p<0.01).The pharmaceutical intervention improved the abnormal changes of every index in model groups in different degree.Among them,genetic expression of GAD67 and GAT-1 in the high-dose TCM group up-regulated significantly.There was obvious difference between the model groups and the western medicine group,high-dose TCM group and middle-dose TCM group in the upregulation of genetic expression of GAT-3(p<0.05,p<0.01,p<0.01 respectively).Meanwhile,the latter three groups up-regulated genetic level of GABAA?5 greatly(p<0.05).There was no statistical difference in the regulation of improving every index in the low-dose TCM group.Conclusion:Modified Ti Fu Kang can regulate and control the anabolism pathway of GABA and keep the normal levels of mRNA transcription of transporters GAT-1,GAT-3 and critical synthetase GAD67 of GABA after the stimulation of sleep deprivation with MMPM.It can also inhibit the receptor mRNA expression of GABAA?5 and decrease the GABA inhibiting action to keep Glu-GABA in a balance to protect the cognitive function of rats with mental fatigue from harm.SummaryAbove all,firstly,the core pathogenesis of mental fatigue is liver stagnation and spleen deficiency.Therefore,the treatment principle is soothing liver and strengthening spleen,regulating qi and relieving depression.Secondly,determine the method of establishing animal model of mental fatigue by sleep deprivation with MMPM for 72 hours.Thirdly,modified Ti Fu Kang can inhibit specific binding between GABA and receptor of GABAA to keep the dynamic balance of Glu-GABA and improve cognitive function of rats with mental fatigue through the regulation of transferring and metabolic pathway of GABA.It verified the core pathogenesis of liver stagnation and spleen deficiency. |
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