| A large number of studies have found that the induction and development of menopausal syndrome(MPS)is closely related to stress caused by various social and psychological factors,and not only the result of hormone changes in the body.Under the joint action of inner stressors and external stressors,which separately are the change of estrogen level and social living environment and psychological factors,the stress regulation function of organism appears disorder.The steady-state balance of hypothalamus-pituitary-varian axis(HPO axis)was broken,resulting in a series of corresponding changes involving neuroendocrine,psychological regulation,metabolic activities,etc.Then a group of symptoms and signs mainly including autonomic nervous disorders will appear,which we call it Menopausal syndrome.Chinese medicine has the advantages of remarkable curative effect and strong safety in the prevention and treatment of menopausal syndrome,but its biological mechanism is not very clear,and the clinical research is lack of sufficient evidence because of the method problem.It has been found thatmitochondrial endoplasmic reticulum structure coupling is closely related to calcium signal regulation,mitochondrial morphological regulation,endoplasmic reticulum stress,neurodegenerative diseases,and so on.It may play a key role in the pathogenesis of MPS.ATF-4 c-Jun is an important regulatory factor for mitochondrial and endoplasmic reticulum stress.In this paper,the relationship between menopausal syndrome and stress was further investigated by literature,clinical and experimental studies.Based on the mitochondrial endoplasmic reticulum structure coupling,the mechanism of the effect of traditional Chinese medicine on the treatment of menopausal syndrome was discussed based on the structure of mitochondrial endoplasmic reticulum.To provide a reliable basis for clinical prevention and treatment of this disease.Stress is divided into psychological stress and physiological stress,and emotional disorder is one of the main manifestations of psychological stress.This thesis combed the researches relating stresssituation and emotional disorders of menopausal syndromethrough the review of related literature at home and abroad,and conducted a Meta-analysis of RCT in coordinating heart and kidney medicines treating emotional disorders of menopausal syndrome.With improved Kupperman questionnaire,group psychological stress questionnaire and TCM syndrome questionnaire as research tools,the clinical part researched 40 to 60 years-old menopausal syndrome patients,fingdingthat the late perimenopausal and postmenopausal women's psychological stress and coping capacity have significant differences,psychological stress levels is correlating with menopausal syndrome illness weight and TCM syndrome.The experimental research,based on mitochondria and endoplasmic reticulum coupling steady stateof HPO axis in the menopausemodel rats,discussed the influence of coordinating heart-kidney medicine "Ning Geng Dan" on the stress state of model rats.It was concluded that "Ning Geng Dan" can adjust the neuroendocrine network of menopause model rats,relieve stress damage,helps restore the mitochondria and endoplasmic reticulum of HPO axis coupling steady state,which is one of the key targets for the treatment of menopausal syndrome.Clinical studyObjectTo explore the correlation between psychological stress and menopausal syndrome and TCM syndrome.MethodsAccording to the experience of clinical practice and referring to the professional guidance and teaching materials,choosing 40 to 60 years old menopausal syndrome patients in Dongzhimen Hospital,gynaecologists filled in general information,improved Kupperman questionnaire,group psychological stress questionnaire and the questionnaire of syndromes.Effective questionnaire data were compiled in Excel spreadsheets,which were divided into two groups of late perimenopausal and postmenopausal according to the menstrual conditions.The researchers extracted and analyzed all the information and data with SPSS 20.0.The above data were tested with t-test,chi-square test,rank sum test and linear regression analysis.The statistically significant difference of all tests was defined P<0.05.Results1.Hot flashes,insomnia and fatigue are the most common symptoms of MPS besides irregular menstruation.Among the cases,the KI scores of heart and kidney disjunction syndrome and kidney yin and yang deficiency syndrome were the highest;in the late menopausal period there were more heart and kidney disjoint syndrome and liver and kidney yin deficiency syndrome,and more kidney yin and yang deficiency syndrome and spleen and kidney yang deficiency syndrome in perimenopausal period.Postmenopausal patients were more severe in the overall prevalence of MPS than in peri-menopausal patients.2.Women before and after menopause bear a heavy psychological and emotional burden,but their cognition and coping style to adverse events and emotional feelings are positive,and postmenopausal women bear more life pressure and bad emotions than women in peri-menopausal period.In general,postmenopausal women suffer greater psychological stress than peri-menopausal women,and the degree of psychological stress of menopausal women is also related to their professional and educational level.3.The degree of psychological stress and severity of disease of women before and after menopause are related to TCM syndrome;the degree of psychological stress was more serious in patients with heart and kidney disconnection and deficiency of kidney yin and yang.4.The total score of psychological stress and KI were negatively correlated with the level of serum E2,and the total score of KI was positively correlated with the level of serum FSH.The lower the estrogen level of the internal stress source,the stronger the degree of psychological stress and the more serious the stress response.Somatic symptoms also became more pronounced.On the other hand,somatic symptoms affect psychological stress and emotional experience,and the degree of psychological stress also affects the secretion of gonadal hormones.ConclusionThe psychological stress state and coping ability of perimenopausal and postmenopausal women were significantly different,and the level of psychological stress was correlated with the severity of menopausal syndrome and TCM syndrome.Experimental studyObjectTo explore the effect of coordinating heart and kidney herbal medicine on the neuroendocrine system,mitochondrial endoplasmic reticulum coupling steady-state and mitochondrial energy metabolism in the HPO axis of climacteric rats.Methods1.Experiment 1:30 natural aged rats(aged 12-13 months)and 40 young rats(aged 3 months)were divided into seven groups with ten rats in each:young rat group,aging blank group,aging Chinese medicine group,aging western medicine group,castration blank group,castrated Chinese medicine group,castrated western medicine group.Castration blank group,castrated Chinese medicine group and castrated western medicine group were ovariectomized rats.The traditional Chinese medicine group was given "Ning Geng Dan",and the western medicine group was given estradiol valerate(Bujialao)for intervention.Blank group was given normal saline After 4 weeks,the rats' uterus/ovary index was measured and the uterus and ovary were observed by HE staining.Serum E2/FSH/LH/NA/5-HT,/?-EP levels were detected by Elisa,and all the data was analyzed by SPSS 20.0.2.Experiment 2:Experimental animals,model and group administration were the same as experiment 1.The hypothalamus,pituitary and ovary of the rats were removed after 4 weeks of administration.The levels of ATF-4 and c-jun in various tissues were measured by Western Blot.The expression of Parkin mRNA,ATF-4 mRNA and c-jun mRNA was detected by fluorescence quantitative PCR.3.Experiment 3:70 young rats were selected and given ovariectomized or ovariectomized with chronic restraint.They were divided into seven groups:young rat group,castration blank group,castrated Chinese medicine group,castrated western medicine group,castration plus stress blank group,castration plus stress Chinese medicine group and castration plus stress western medicine group.There were 10 rats in each group.The mitochondria were prepared from hypothalamus,pituitary and ovary of rats after 4 weeks of intervention.The activity of Na-K-ATPase and Ca 2-Mg 2-ATPase was measured.SPSS 20.0 software was used to analyze the data.Results1.The results of the first batch of animal research showed that,compared with the young rat group,serum E2 levels of castration blank group and aging blank group were significantly decreased,with a significant rise in FSH levels.Serum NA,5-HT and beta EP levels were significantly reduced in castration blank group and 5-HT level decreased significantly in aging blank group comparative to the young rat group."Ning Geng Dan" could increase the serum E2/5-HT and decrease serum FSH/LH levels significantly,and had the trend to increase the levels of NA and ?-EP.2.The results of experiment 2 showed that the content of c-Jun in hypothalamus of castrated blank group was slightly higher than that of young rat group,and the content of c-Jun in hypothalamus of castrated Chinese medicine group and ovariectomized western medicine group was lower than that of castrated blank group and aging blank group.The content of c-Jun in hypothalamus of Chinese medicine group and western medicine group was close to that of young rat group,the content of ATF-4 in hypothalamus in castrated blank group was lower than that in young mouse group,and the ATF-4 content in castrated Chinese medicine group and ovariectomized western medicine group was slightly higher than that in castrated blank group.The content of ATF-4 in hypothalamus of aging blank group was higher than that of young rat group,and that of aged Chinese medicine group and aged western medicine group was lower than that of aged blank group.The expression level of c-Jun in ovary was similar in castrated blank group,castrated Chinese medicine group,castrated western medicine group,aging blank group,aging Chinese medicine group and aged western medicine group,and was slightly lower than that in young mice group.The content of ATF-4 in ovary of ovariectomized Chinese medicine group and ovariectomized western medicine group was lower than that of young rat group,and that of aging blank group was slightly higher than that of young mouse group,and that of aged Chinese medicine group and aged western medicine group was slightly lower than that of old blank group.3.The results of experiment 2 showed that the expression of Parkin mRNA and ATF-4 mRNA in hypothalamus,pituitary and ovary of aged rats was significantly higher than that in young rats(P<0.05),and the expression of c-jun mRNA in hypothalamus and pituitary was decreased.The expression of c-jun mRNA in ovary decreased significantly(P<0.05).Compared with the young rats,the levels of Parkin mRNA and ATF-4 mRNA in hypothalamus,pituitary and ovary of castrated rats were significantly decreased,the expression of c-jun mRNA in hypothalamus and pituitary were significantly increased,and the level of c-jun mRNA in ovary was significantly decreased.4.The results of experiment 2 showed that,compared with the castration blank group,the levels of Parkin mRNA in pituitary and the hypothalamus of the castrated Chinese medicine group and the ovariectomized western medicine group were significantly increased(P<0.05),the level of ATF-4 mRNA in pituitary was significantly increased(P<0.05),the level of c-jun mRNA in hypothalamus of castrated Chinese medicine group was significantly decreased(P<0.05).Compared with the aged blank group,the levels of Parkin mRNA in hypothalamus,pituitary and ovary were decreased in the aged Chinese medicine group and aged western medicine group(P>0.05),the level of ATF-4 mRNA in hypothalamus and pituitary was decreased(P>0.05),and the level of ATF-4 mRNA in ovary was significantly decreased(P<0.05).The expression of c-jun mRNA in hypothalamus,pituitary and ovary of aged rats was not significantly affected by Chinese and western medicine.5.The results of experiment 3 showed that,compared with the young rats,the activity of the Ca2+-Mg2+-ATP enzyme in the ovary and the two enzymes in the hypothalamus and pituitary of the mitochondria of the castrated blank group and the castrated stress blank group decreased significantly(P<0.05).Compared with the castrated blank group,the activity of mitochondrial Ca2+-Mg2+-ATP enzyme in the hypothalamus of the castrated stress blank group was significantly reduced(P<0.05)."Ning Geng Dan" and estradiol valerate can increase the activity of two enzymes in the hypothalamus of ovariectomized rats and ovariectomized rats,two enzymes in the pituitary mitochondria of ovariectomized rats,the Ca2+-Mg2+-ATP enzyme of pituitary mitochondria in ovariectomized stress rats,and Ca2+-Mg2+-ATP enzyme in the ovary mitochondria of ovariectomized rats,and there is no significant difference between Chinese and Western medicine.ConclusionStress damage is an important pathological mechanism of menopausal syndrome.The coordinating heart and kidney prescription "Ning Geng Dan" can adjust sex hormones and neuroendocrine network of menopausal rat model,help restore the mitochondria and endoplasmic reticulum coupling steady state of hypothalamus-pituitary-ovarian reproductive axis and relieve stress injury of menopausal rat model. |
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