| This research was a part of the item supported by fund for research project ofnational natural science foundation of China, No:30271567.Background:Anger is one of the seven emotion. It has frontal and negative effectiveness. In thenormal circs,it was the reflection of the human spirit state to impersonality things, butonly when abrupt, violent, perennial perdure stimulate emotion ,or the liverphysiological function which was very consanguineous with anger was abnormity, itexceeded its physiological modulatory extension, it caused by emotional upsets ofZangfu to perform its dispering function, made imbalance of Yinyang and disorder ofQi and derangement of qi and blood, caused many of diseases. Sush as《LingShu·ShouYaoGangRou》indicated that: "emotional pathogenic factorsimpairing Qi, and Qi impairing the Zang, then it become the illness-syndrome."point out that sorrow, fear and anger generally impairing the activities of qi ofdemic, caused derangement of the activities of qi and suffered disease from fivesolid organs. Anger could result in the illness being occurred. So it was one of thefactors which induced internal injury and intricate illness.modern medicine figured, hippocampus, hypothalamus, almond in the cerebralfringe system was the emotion form and modulatory center.It maintained theseif-steady condition of the inner environmental,and was the adjustment andcontrol center which liver controlled the catharsis function.《Internal Classic》indicated that: "rage impairing the liver." means a morbid condition of adverse of the liver-qi leading to the uprising of the blood ,caused by great rage resulting ininfluencing the physiological function of the liver.Traditional Chinese medicineconsider that the liver being in charge of flourishing and up-stirring of theliver-wind. Rage is a specified emotion come from the liver. Anger has tightlyassociation with liver. From the view of the research production in modernphysiology and pathology about the liver, the physiological function and pathologicalchange related to several systems in the human.Some research indicated,liver illnesssymptoms which Chinese traditional medicine discussed might concurred thefunction change of the nerve,incretion and immunity system. For example,whenliver was depressed, some indexes changed,such as central neurotransmitters:noradrenalin, adrenalin, 5-HT, dopamine, skin electricity, hormone in the blood:catecholamine, adrenal organise structure ,the immunity system: CD4+/CD8+, atthe same time ,the sympathetic nerve was excessive. It was suggested that the liverfunction discussed in Chinese traditional medicine was correlative with the nerve-ineretion-immunity system network discussed in modern medicine. Therefore,in the whole ,the nerve biology mechanism which liver controlled the catharsisfunction was correlative with the modulation of the hypothalamus-pituitary-adrenalgland axis.It might concretely correlate with many central neurotransmitters andtheir synthesize enzyme, neuropeptide, hormone, cyclic nucleotide acid system,andthe change of c-fos mRNA and its protein expression in the course of the adjustingchronic mentality stimulus reaction,such as the emotion abnormal activity.This research was going to determine and analyse the the contents ofmonoamine neurotransmitters such as E,NE,DA and their metabolite inhypothalamus of rats with anger stress by HPLC-ECD,and discussed themodulation of TianMaGouTeng Decoction to monoamine neurotransmitters inhypothalamus. Using a single emotion stimulate to the influence of the centerneurotransmitters ,We were going to analyse the interaction and relation aboutmonoamine neurotransmitters in the modulation of HPA, look after an objectivie index which had most significent difference, probe into the mechanisms which thenerve centre changed with anger stress, provide the experimental testimony inpreventing and treating the psychology disease with Chinese traditional medicine.Methods:1. According to Megan's method, the animal model of anger emotion similar tohuman was set up.32 male rats were divided into three groups by random with 8 ratsin each group. There were normal group, anger model group and lonely breedinggroup, while the invading group was set in addition. The anger model group was setup as follows: the rats were breeding in stainless steel cage (50×30×20cm), anddrink and eat randomly. To make reverse Day and Night, the lamp was turned on at24:00 at night, and was turned offat 12:00 at noon. During 13:30-15; 30 in 11th day,the rats were excited. At the time, 1 rat of the invading group was put into the cage.The behavior of the rats was recorded during 6~20min.At 21min, the rat of modegroup was taken out offthe cage, and put into experiment case of open-field test. Thebehavior after stress was detected.Under the same environment, rats of normal mode group were bred together.Drink and fed randomly. At 11th day the behavior was detected and open-field testwas carried out. Rats in the lonely breeding group were fed lonely for 10 day, whileno anger excitement was given at 15:00 in 11th day. The behavior was recorded andscored. At 15:30 the rats were put into experiment case of open-field test. Thebehavior after stress was detected. Rats of the invading group were fed togther, andwas given drink without food.2. 32 male rats with weights of 180~220g were divided into three groups byrandom with 8 rats in each group. There were normal group, anger model group andlonely breeding group, while the invading group with 8 rats was set inaddition. The anger model group was treated as above. TianMaGouTengDecoction was given to rats of this group by intragastric administration for 3 days with 2mL for one day at a time. The normal group was fed together, with randomdrink and food for 10 days and without excitement. In 11th day, all the rats wereexecuted. Hypothalamus was got and homogenated, and then centrifugated.monoamine neurotransmitters and their metabolites were quantitated by HPLC withelectrochemical detector.Statistical analysis:Statistical analysis was performed on software SPSS13.0. The relationship oftwo variables in openfield test was analyzed by the method of Pearson correlation. Bythe method of One-way ANOVA means between several samples were compared.And then, the methods of Least-significant difference (LSD) and Dunnett were usedfor comparison between two samples. A difference was considered statisticallysignificant only at 95% confidence interval or higher (P<0.05).Results:1,The establishment and evaluation of the animal model of anger stress(1) The behavior score of rats in model groupEach indicatrix and the total score were analyzed by Pearson correlation. Therewas significant deviation between total score and Attack fights, Threats, Mounting(P<0.05).(2) The behavior score of rats in model group of anger stress in open-field testSignificant deviation existed in the crossing score, rearing score and open-fieldtest score of each group (P<0.01). The score of model of anger stress wassignificantly higher than the lonely breeding group and the normal group (P<0.01).There was positive correlation between crossing score and rearing score, with r=0.876and P=0.000.(3) The score of rats in model group of anger stress in open-field testSignificant deviation existed in retention time, modify frequency, modify timeand feces grain (P<0.01). Compared with normal group, the retention time of themodel group of anger stress was longer (P<0.01), the modify time of the model group of anger stress was shorter (P<0.01).The feces grain was more than normal group andlonely breeding group (P<0.01). But the deviation of modify frequency was notsignificant between the normal group and the model group of anger stress (P>0.05).There was positive correlation between modify time and modify frequency, withr=0.665 and P=0.000. And there was positive correlation between the total score inopenfield test and feces grain, with r=0.564 and P=0.004.2,Effects of anger stress on contents of monoamine neurotransmitter and theirmetabolite in hypothalamus of rats and the modulation function of the traditionalChinese medicine TianMaGouTeng Decoction.Compared with normal group, The contents of NE,DA and theirmetabolite5-HIAA, had been risen singnificantly in model rats (p<0.01);Compared with model group, TianMaGouTeng Decoction could reduce the contentsof NE,DA and their metabolite DOPAC, 5-HIAA(p<0.05),but could increase thecontents of 5-HT(p<0.05). The contents of E,MHPG and HVA had no significantdiscrepancy (P>0.05).Conclusions:1.This animal model was an ideal model of anger stress to emotion,and themethod feasibility of evaluating the model was better.2.When rats was stimulated with anger stress, the contents of monoamineneurotransmitters in hypothalamus such as NE,DA and their metabolite 5-HIAAwas increased distinctly.3. The traditional Chinese medicine compound, TianMaGouTeng Decoction couldreduce the contents of monoamine neurotransmitters in hypothalamus such asNE,DA and their metabolite DOPAC, 5-HIAA,but could increase the contents of5-HT.4. Anger stress to emotion could activate the hypothalamus-pituitary-adrenal glandaxis,and make it be excessive.It brought monoamine neurotransmitters to a confusivestate. TianMaGouTeng Decoction could modulate this confusive state in some extent. |