The Effect Of Liver Soothing And Kidney Tonifying Method On The Behavior And The Expression Of P38mapk/erk5 In Hippocampus Of Rats With Liver Depression Syndrome Of Perimenopause Syndrome

Objective:To study the effects of liver soothing and kidney tonifying method on behavior and MAPK signaling pathway of rats with liver depression syndrome of perimenopause syndrome,explore the molecular biological mechanism of liver depression syndrome of perimenopause syndrome,and provide part of experimental basis for the diagnosis of"liver depression syndrome"of perimenopause syndrome.Methods:The estrous cycle of the rats was observed by HE staining method of vaginal ablated cells,and the perimenopause was determined.The rats entering perimenopause were set up with chronic bondage method for 3 weeks to establish the model of liver depression syndrome of perimenopause syndrome.Objective the hypothalamic-pituitary-adrenal axis（HPA）axis and behavioral score were used to determine The success of The liver depression model.Randomized group:blank group,liver depression model group,liver dredging and kidney tonifying group.After 3 weeks of intervention with traditional Chinese medicine,the effects of liver soothing and kidney tonifying method on weight and behavioral scores of rats were compared.Using ELISA method to detect each group rats serum Estradiol（E₂）,Dopamine（DA）,5 hydroxytryptamine（5-HT）,tumornecrosisfactoralph（TNF-α）,Interleukin6（IL-6）,beta-endorphin（β-EP）concentration and analyze the difference between groups.The effect of quantitative real-time PCR（qPCR）on the expression of p38 mitogen-activated protein kinases（p38MAPK）and extracellular signal regulated kinase（ERK5）in rats was studied.Results:1.After 8 days of smear observation on vaginal exfoliated cells of 12 months old female rats,it was found that the estrous cycle was irregular and there were frequent interestrous periods with a large number of white blood cells.After 3 weeks of chronic bondage,it was generally observed that the weight of rats decreased significantly,their behavior was slow,their reaction was slow,their hair was dry and dull,and they liked to bury their heads in the corners.2.After 3 weeks of intervention with traditional Chinese medicine,the preference degree of sugar water in the shugan bushen group was higher than that in the liver depression model group.In the open-field experiment,the horizontal activity,central residence time,upright frequency and modification frequency of rats in the shugan bushen group were higher than those in the liver depression group.3.Three weeks after the intervention,corticosterone（CORT）and adrenocor ticotropic hormore（ACTH）levels in the liver depression model group were increased compared with the blank group,while the difference was statistically significant（P<0.05）.Compared with the liver depression model group,the levels of CORT and ACTH were decreased in the liver soothing and kidney tonifying group,and the CORT levels were statistically different（P<0.05）.However,there was no significant difference in ACTH（P>0.05）.Corticotropin releasing-hormone（CRH）was increased in the liver depression group,but there was no systemic difference in CRH（P>0.05）.Compared with the blank group,the levels of E₂,β-EP,DA,and 5-HT in the liver depression model group decreased significantly（P<0.05）.Compared with the liver depression model group,the indexes of liver dredging and kidney tonifying group were all increased,with statistical differences in 5-HT andβ-EP（P<0.05）.Compared with the blank group,the levels of inflammatory cytokines TNF-αand IL-6 in the liver depression model group were significantly increased,with statistical difference（P<0.05）.Compared with the liver depression model group,the levels of TNF-αand IL-6 were decreased in the liver soothing and kidney tonifying group,with statistically significant difference（P<0.05）.4.The expression levels of p38MAPK and ERK5 genes in the hippocampus of each group were detected by qPCR.Compared with the blank group,the expression levels of p38MAPK were increased in the liver depression model group,with statistically significant difference（P<0.05）.Compared with the liver depression model group,the expression of p38MAPK was decreased in the liver soothing and kidney tonifying group,and the difference was statistically significant（P<0.05）.Compared with the blank group,the expression of ERK5in the liver depression model group was decreased,and the difference was statistically significant（P<0.05）.Compared with the liver depression model group,the ERK5 expression increased in the liver soothing and kidney tonifying group,showing a statistical difference（P<0.05）.Conclusion:1.Liver soothing and kidney nourishing method may inhibit hyperactivity of HPA axis,increase the secretion and synthesis of monoamine neurotransmitters,improve the level of estrogen E₂,enhance the function of immune system,reduce the inflammatory reaction of the body,and thus increase the behavioral activity of rats and improve depression-like behavior.2.Liver soothing and kidney tonifying method may reduce the expression of p38MAPK and increase the expression of ERK5 in the hippocampus of rats with liver depression syndrome of perimenopmenopausal syndrome,inhibit the secretion of inflammatory cytokines,improve the damage of nervous system,and thus improve depression-like behavior.