The Effect Of Physical And Psychological Stress On The Pathogenesis Of HPRL And The Study On The Mechanism Of Central Dopamine ERK Signal Pathway Intervention By The Method Of Soothing The Liver And Strengthening The Spleen

Objective:1.By the investigation of hyperprolactinemia to discuss the effect of constitution and psychological stress on the disease,and providing clinical basis for the prevention and treatment of the disease2.Using the modified Xiaoyaosan prescription to explore the effect of soothing liver and activating spleen method on the central dopamine receptor ERK signal transduction pathway in hyperprolactinemia rats,so that it can elucidate the effect of this method on HPRL to enrich the pathogenesis and treatment of it.Methods:1.Separating the crowd who accordance with the inclusion criteria into the control group(normal childbearing age women)and the hyperprolactinemia group.Investigating respondents by using habitus Decision table and psychological stress self-rating scale.Also,using SPSS 18 statistical software to collect information and analysis it.2.By using pituitary transplantation to produce hyperprolactinemia rats.It randomly divide into 12 groups,which are control group,model control group,bromocriptine group,DIR antagonist group(SCH23390 group,SCH23390+TCM group,SCH23390+bromocriptine group),D2R antagonist group(haloperidol group,haloperidol+TCM group,haloperidol+bromocriptine group),TCM treatment group(low-dose group of Chinese medicine,middle-dose group of Chinese medicine,and high-dose of Chinese medicine group).After 30 days' treatment,using Western blot to detect hypothalamus of rat models,which is the expression of Ras,Raf and ERK1/2 protein.Also,by using immunohistochemistry to detect the influence of the prescriptions on the hypothalamic ERKI/2 level of HPRL rat model,and detect the influence of the drugs on rat hypothalamic MEK1/2 gene expression of ERK1/2 and HPRL model by using Real Time-PCR method.Results:1.The age of HPRL patients which are ranged from 21 to 34 years old,and it account for 81%of the total.2:The results of investigating habitus,belong to balanced constitution is(37.1%)in the control group,and HPRL group is(15.5%)(p=0.001<0.01).Qi-stagnation constitution in control group is(10.5%),and Qi-stagnation constitution is(21.3%)(p=0.01 7<0.05)in HPRL group.Yang deficiency constitution in the control group is accounted for(7.6%),at the same time,it is(16.5%)(p=0.049<0.05)in HPRL group.There is no significant difference in the distribution of the other type of-constitution.3,Psychological stress:According to compare the control group with the HPRL group,the HPRL group is significantly more than the control group(p=0.005<0.01),(p=0.029<0.05)in the negative of people's life in work and study.4,The results of animal experiment:comparing the blank control group with model control group,the Ras,Raf,MEK1/2,ERK1/2 content of model control group are decreased significantly.In the absence of antagonist,comparing with the model control group,the dose of Ras,Raf,MEK1/2 and ERK1/2 could be increased in all dose groups of TCM.In addition,relationship between dose and effect,which are exist in every dose groups of TCM.Using the antagonism of DIR compare with the model group,SCH23390 group Raf,and Ras expression quantity are slightly went up.Comparing with the SCH23390 group,Ras,Raf,MEK1/2 and ERK1/2 could be increased in SCH23390 combine TCM group(P<0.01),SCH23390 combine bromocriptine group can increase Ras(P<0.05),and Raf,MEK1/2,ERK1/2(P<0.01).Also,MEK1/2,ERK1/2 expression are increased significantly.Compared with the SCH23390 combine TCM group,the ERK1/2 level in the SCH23390 combine bromocriptine group was much lower than that in the combine TCM group(P<0.01).The Ras,Raf protein expression in antagonistic D2R,and haloperidol group are decline,and the expression MEK1/2,ERX1/2 are significantly decreased(P<0.01).Comparing with the haloperidol group,Raf could be increased(P<0.05),MEK1/2 and ERK1/2 are increased significantly in haloperidol combine TCM group(P<0.01),Ras could be increased(P<0.05).Compared with the haloperidol combine bromocriptine group,MEK1/2 and ERK1/2 are increased significantly in haloperidol combine TCM group(P<0.01).Conclusion:1.This distribution accords with HPRL,which is mostly occurring in women age in 21to34.2,Healthy women are mostly in balanced constitution,and the susceptible physical types of HPRL patients are mainly in qi-stagnation constitution and yang deficiency constitution.3,The incidence of HPRL is associated with negative of people's life,work and study.4,The effects of TCM on hypothalamic dopamine ERK pathway play a role of the promotion.The concrete mechanism is that xiaoyaosan can excite dopamine D2R,inhibite dopamine D1 R,to regulating the ERK/MAPK signal pathway,reduce the secretionof PRL,is one of the mechanisms for the treatment of HPRL,Compared with inhaloperidol combine TCM group,fluoride+bromine group increased MEK1/2mRNA and ERK 1/2 far less than fluoride+group(P<0.01).