| ObjectiveTo prevent HPRL in advance and introduce psychotherapy to HPRL patients with liver qi stagnation, this study analysed the mental status and character traits of HPRL patients with liver qi stagnation through the Eysenck Personality Questionnaire and the State—Trait Anxiety Inventory;Based on Seven Emotions and psychological stress theory, this study attempted to explore animal model of HPRL caused by liver qi stagnation to provide theoretical evidence to regulate the syndrome differentiation of Traditional Chinese Medicine(TCM). It also attempted to discover the etiology and pathogenesis of HPRL caused by liver qi stagnation, by comparing the traditional HPRL model with liver qi stagnation in an animal model triggered by psychological stress on both behavior study and the neuroendocrine system.Method1.Method of clinical studyGroup A:28 HPRL(PRL≥30ng/ml) patients with liver qi stagnation; Group B:30 liver qi stagnation patients with menstrual disorders and/or infertility; Group C:25 normal people.The sex hormones of patients diagnosed with liver qi stagnation who also have menstrual disorders, infertility, or galactorrhea, were tested with chemiluminescence immunoassay during the first three days of the menstrual cycle at 9:30-10:30am. According to PRL value, inclusive and exclusive criterions, these patients were divided into A and B groups. Subjects in Group C are from the Physical Examination Center during the same period. Both Group A and Group B would be estimated on the degree of liver qi stagnation. Groups A, B and C filled in the Eysenck Personality Questionnaire(EPQ) and State—Trait Anxiety Inventory(STAI-Form) within 30min. The EPQ was filled in with "Yes" or "No" answers and transformed into T scores with Psychoticism(P),Neuroticism(N), Extroversion(E) and Lie(L) dimensions by EPQ adult test software 5.0. The STAI-Form included a State Anxiety and Trait Anxiety form, and each of them included 20 questions.2. Method of experimental study37 specific pathogen free (SPF) SD female rats, weighing 200g±20g, were divided into four groups randomly at different weight levels after raising for one week Group A:Liver qi stagnation group with 11 ratsGroup B:Liver qi stagnation+metoclopramide group with 10 ratsGroup C:Metoclopramide group with 8 ratsGroup D:Control group with 8 ratsModel preparation:From the 8th day, Groups B and C received a metoclopramide subcutaneous injection in the amount of 62.5mg per kilogram of body weight daily for 8 days. In the mean while, Group B also received 5 kinds of unpredictable psychological stress for 21 days with Group A.The general condition of each group was observed, such as defecation, mental condtion, activity and weight. After the last stimulation, all the rats were deprived of food, but received their normal water supply for 12 hours. The rats were weighed, and between 9:30-10:30 am the rats'heads were removed under 10% chloral hydrate anaesthesia on the 29th day. Blood serum was kept at -80℃to test the sex hormones. The hypothalamus was seperated on ice, and after being weighed, was kept at -80℃to test monoamine neurotransmitters such as noroepinephrine(NE) and 5-hydroxytryptamine(5-HT). Result1. Results of clinical research(1) Sex hormone comparison:The serum value of both E2 and FSH in HPRL patients with liver qi stagnation (Group A) was lower than in liver qi stagnation patients with menstrual disorders and/or infertility (Group B) (p <0.05), while that of PRL in Group A was significantly higher than in Group B (p<0.01).Both serum values of FSH and T showed no statistical difference (p>0.05). (2) Comparison of liver qi stagnation scoring and age:It showed that the liver qi stagnation scoring in both Group A and Group B showed no difference (p>0.05). And among Groups A,B and C, it showed no age difference (p> 0.05)(3) EPQ analysis:It showed no difference in Lie(L) among these three groups (p>0.05). Compared with Group B, Group A had significantly higher scores in Psychoticism(P) and Neuroticism(N) (p<0.01), and no statistical difference in Extroversion(E) (p>0.05). Compared with Group C, Group A had ssignificantly higher scores in P and N (p<0.01), and lower scores in E (p <0.05). Compared with Group C, Group B had higher scores in N (p<0.01) and lower scores in E (p<0.01), while there was no difference in P (p>0.05)(4) Anxiety comparison:Both State Anxiety and Trait Anxiety scoring were higher in Groups A and B than in Group C (p<0.05). Both State Anxiety and Trait Anxiety scoring was higher in Group A than in Group B (p<0.01)2. Results of animal experimental study(1)Behavioral observation:As time passed by, dodge, slackness, looser stools, and matte fur were observed among rats in Groups A and B, while only calm, somnolence and lacking in strength were observed in Group C. Anxiety and overreaction to the stimulator appeared in both A and B groups, but not the C group.(2)Weight comparison:Before any stimulation, the weight of the rats in all four groups showed no statistical significance (p>0.05).In the total 21 days the weight of the rats in Groups A and B grew more slowly than in Groups C and D, while in Groups C and D there was no change in weight (p>0.05). It also showed that the rats in Group A grew more slowly than those in Group B (p<0.05)(3)Sex hormone comparison:After the experiment the serum value of PRL in Groups A,B and C was higher than in Group D (p<0.05), while it showed no difference among Groups A,B and C (p>0.05).The serum value of both E2 and FSH in Groups A,B and C was significantly lower than in Group D (p< 0.01), while that of both sex hormones showed no difference among Groups A,B and C (p>0.05)(4)The comparison of the concentration of hypothalamic monoamine neurotransmitters:NE concentration in Groups A,B and C was significantly lower than in Group D (p<0.01),while that of 5-HT was higher in Groups A and B than in Groups C and D (p<0.01). NE concentrations among Groups A,B and C showed no significant difference (p>0.05).5-HT concentrations in Groups A and B showed no significant difference (p>0.05) and in Groups C and D showed no significant difference either (p>0.05) Conclusion1. Clinical research suggested that HPRL patients with liver qi stagnation tend to have high levels of both state anxiety and trait anxiety. In the disposition aspects, HPRL patients tend more toward introversion, neuroticism (which includes mood swings, anxiety, worry, depression, and unreasonable behavior caused by overreaction), and psychoticism (loneliness, lack of sympathy, lack of empathy, slow reaction time, hostility, etc.). And high scores on psychoticism may be the unique characteristic of HPRL patients.2. The liver qi stagnation model triggered by psychological stress has the same PRL, FSH and E2 levels compared with the traditional metoclopramide model and the two combined HPRL animal model. And according to the Seven Emotions Theory of Chinese medicine and physiological-psychological-social mode of modern medicine, the former model is a more feasible way in the study of HPRL which exibites liver qi stagnation. And its behavior, weight change and changes in neurotransmitters also conformed the clinical manifestation of liver qi stagnation patients. It also indicated that the liver qi stagnation model triggered by psychological stress could be one of the substantial causes of HPRL.3. The changes in neuroendocrine network can be seen in HPRL models caused by liver qi stagnation. The changes of hypothalamic monoamine neurotransmitters can be seen in both HPRL models caused by liver qi stagnation and by metoclopramide injection, which were NE reduction and 5-HT increase in HPRL models caused by liver qi stagnation and only NE reduction in HPRL models caused by metoclopramide injection. Thus it can be seen that the onset of HPRL has a close relationship with emotional stimulation and its possible mechanism is the stress that causes the disorder of the central neurotransmitters by stimulating the central nervous system. The neurotransmitters cause the disorder of the sex hormones by influencing the hypothalamic-hypophysical-sex gland axis.
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