Study On Liver-qi Stagnation And Its Mixed Syndromes Characteristics Of Perimenopausal Period Syndrome And Its Molecular Biological Basis

Perimenopausal period syndrome(PPS) is a syndrome that women in menopause, estrogen levels drop, causing neuroendocrine dysfunction, decreased immune function and autonomic nervous system dysfunction. Liver-qi stagnation is an important pathogenesis of PPS. In this studv the method of syndrome element differentiation is used to research characteristics of Liver-qi stagnation and its mixed syndromes, the relationship between former.autonomic nervous system dysfunction symptoms.monoamine neurotransmitter and gene polymorphisms is explored to find the molecular biologic material basis and genetic susceptibility of Liver-qi stagnation and its mixed syndromes. The puipose is to deepen the understanding of the pathogenesis of liver-qi stagnation of PPS. while providing an objective basis for early diagnosis and prevention of liver-qi stagnationt of PPS.Part I Study on the distribution characteristics of syndrome element of PPS,the correlation between PPS common symptoms and liver-qi stagnation and its mixed syndromesObjective:To analyze the TCM disease location and nature of PPS, and the characteristics of liver-qi stagnation and its mixed syndromes, explore the relationship of most common symptoms of autonomic nervous system dysfunction and the former.Methods:459 cases of PPS patients have been observed, relevant clinical information were collected, syndrome element differentiation was used to analyze the laws of TCM disease location and nature of PPS and characteristics of liver-qi stagnation and its mixed syndromes. PPS common syndrome elements were cluster analyzed.which is to explore the relationship of PPS common symptoms and liver-qi stagnation and its mixed syndromes.Results:(1)The top six common symptoms of PPS were paresthesia (64.49%). insomnia (59.48%). irritability (54.68%). dizziness (47.93 percent), bone and joint pain, muscle pain (46.19%). hot flashes sweating (43.57%)(2)Disease location of PPS involved the heart, liver, spleen, lung. kidney. uterus, stomach, gall bladder, large intestine and urinary bladder. The patients with disease location in Liver are most.72.55% (p<0.01). followed by disease location in kidney, spleen and uterus (p< 0.01).(3)The excess disease nature of PPS involved Qi stagnation, phlegm, dampness, blood stasis. heat. cold. Qi stagnation is most 58.39%. followed by phlegm, dampness, stasis (p<0.01)(4)The deficiency disease nature of PPS involved Yin-deficiency,Qi-deficiency. blood deficienty. Yang-deficiency, exuberance of Yang, essence deficiency. Among them Yin-deficiency is the most.69.72%(p<0.01). followed by Qi-deficiency. blood deficiency and Yang-deficiency,(p<0.01). then essence deficiency.(5) The common syndrome elements of PPS cluster display Qi stagnation, blood stasis, phlegm, and the liver classified as a class, Qi-deficiency, Yang-deficiency, blood deficiency. Yin-deficiency, spleen, kidney, dampness as a category, and the rest a category.(6)About the common symptoms of PPS:the incidence of dizziness in liver-Qi stagnation group was lower than the non-liver-Qi stagnation group (p<0.05), but its incidence of bone and joint pain, muscle pain was higher (p<0.05). no difference in the incidence of other symptoms between liver-Qi stagnation and non-liver-Qi stagnation group.(7) The characteristics of mixed syndromes of liver-Qi stagnation in PPS:the main mixed disease location are kidney, spleen and uterus:the main mixed excess disease nature are phlegm, blood stasis, dampness, and hot; the main mixed deficiency disease nature are Yin deficiency Qi deficiency, blood deficiency and Yang deficiency.(8) The characteristics of liver-Qi stagnation and its mixed syndromes of PPS affect its common symptoms:in liver-Qi stagnation with disease location of kidney patients, the incidence of hot flushes, sweating are higher than those whose disease location without kidney (P<0.05); in liver-Qi stagnation with blood stasis patients, the incidence of bone and joint pain, muscle pain was significantly higher than those without blood stasis (p<0.01). incidence of hot flashes, sweating, insomnia higher than those without blood stasis (p<0.05): depression happen more in liver-Qi stagnation with heat than those without heat (p<0.05): the incidence of palpitations is significantly higher in liver-Qi stagnation with qi deficiency than those without Qi-deficiency (p<0.01). urinary symptoms higher too(p<0.05):urinary symptoms were more frequently happen in liver-Qi stagnation with Yin-deficiency than those without Yin-deficiency(p<0.01):urinary symptoms were happen more in liver-Qi stagnation with blood deficiency than those without blood deficiency (p<0.05).Conclusion:1. PPS is the result of multiple Zang-fu organ dysfunction, and disease nature involves cold and heat, excess and deficiency, the main disease location are liver, kidney, spleen and uterus: main excess syndrome are Qi stagnation, phlegm, dampness, blood stasis; main deficiency syndrome are Yin-deficiency Qi-deficiency,blood deficiency. Yang-deficiency. Excess syndrome and liver have close relationship. Deficiency syndrome with kidney and spleen have close relationship.2.Liver Qi stagnation of PPS often with pathological changes in the kidney, spleen and uterus. often happen with phlegm, blood stasis, dampness, heat.Yin deficiency. Qi deficiency, blood deficiency. Yang deficiency Simultaneously3.The features of liver Qi stagnation and its mixed syndromes of PPS affect its performance of PPS autonomic nervous system dysfunction and other symptoms.Part Ⅱ Study on the molecular mechanisms of features of liver Qi stagnation and its mixed syndromes of PPSⅠ. Study on the correlation between neurotransmitters and liver Qi stagnation of PPS Objective:To investigate the relationship between neurotransmitter and the characteristics of liver Qi stagnation and its mixed syndromes of PPS.explore part molecular biology basis of latter.Methods:ELISA methods to detect 189 cases of PPS patients monoamine neurotransmitters (5-serotonin 5-HT. norepinephrine NE. dopamine DA) and β-endorphins(β-EP) in blood.Compare neurotransmitter differences between liver Qi stagnation group and non liver Qi stagnation group, compare the differences between different mixed syndromes.Results:(1)In liver Qi stagnation group.total bilirubin.direct bilirubin.indirect bilirubin was significantly higher than the non-liver Qi stagnation group (p<0.01). Follicle stimulating hormone (FSH) higher than the non-liver Qi stagnation group (p<0.01).(2) Logistic regression based on liver Qi stagnation, independent variables into the equation is the direct bilirubin, giutamyl endopeptidase and alanine aminotransferase (p<0.01).(3) In liver Qi stagnation group.DA and NE were lower than the non-liver Qi stagnation group. (p<0.05)(4)In the group of liver-Qi stagnation with disease location in kidney DA and 5-HT were significantly lower than the group of disease location without kidney (p<0.01):in the group of liver-Qi stagnation with phlegm DA were significantly lower than those without phlegm (p <0.01),5-HT lower too (p<0.05); in the group of liver stagnation with dampness 5-HT was significantly lower than those without dampness (p<0.01):in the group of liver -Qi stagnation with heat 5-HT was significantly lower than those without heat (p<0.01):in the group of liver-Qi stagnation with Qi deficiency 5-HT was significantly lower than without Qi deficiency (p<0.01):in the group of liver -Qi stagnation with blood deficiency DA and 5-HT were significantly lower than those without blood deficiency (p<0.01):in the group of liver-Qi stagnation with Yin deficiency DA and 5-HT were lower than those without Yin deficiency(p<0.05)Conclusion:1. Reduced DA and NE may be molecular basis of liver-Qi stagnation in PPS patients.2. The changes of monoamine neurotransmitter closely associated with the characteristics of liver-Qi stagnation and its mixed syndromes.3.Total bilirubin. direct bilirubin. indirect bilirubin may be molecular basis of Liver-Qi Stagnation of PPS.Ⅱ.Study on correlation between liver-Qi stagnation of PPS and the estrogen receptor gene polymorphismsObjective:To investigate the relationship between ER genotype and liver-Qi stagnation and characteristics of its mixed syndrome of PPS. mining their predisposing factorsMethods:probe method were used to detect the polymorphism of ERa [rs9340799 A/G]. ER(3 [rs1256030 C/T. rs3020444 T/C] in the blood of 189 cases.Results:(1)The frequency of ERβ-rs3020444-TT in liver-Qi stagnation group (85.93%) is higher than non-liver stagnation group (65.57%) (p<0.01). the remaining genotypes-are no difference.The relative risk of Liver-Qi Stagnation of PPS with ERβ-rs3020444 TT genotype is 3.208.(2)In patients with liver-Qi stagnation. Erβ-rs3020444 and Erβ-rs1256030:TT/CC frequencies higher than those of non-liver-Qi stagnation (p<0.05):In patients with liver-Qi stagnation Erβ-rs3020444 and ERα-rs9340799:TT/AG. TC/AG and CC/AG frequencies higher than those of non-liver-Qi stagnation(p<0.05).(3) ERβ-rs3020444 genotypes of the patients of liver-Qi stagnation with dampness and with phlegm respectively were different to without dampness and phlegm (p< 0.05). ERβ-rs 1256030 genotypes of the patients of liver-Qi stagnation with heat and with Qi deficiency were respectively different to without heat and qi deficiency (p<0.05). ERα-rs9340799 genotypes of the patients of liver-Qi stagnation with dampness. Qi deficiency, blood deficiency and Yang deficiency respectively were different to without dampness. Qi deficiency, blood deficiency and Yang deficiency (p<0.05).Conclusion:1. ERβ-rs3020444-TT type may be one of the genetic susceptibility basis of Liver-Qi Stagnation of PPS.2. The susceptibility of Liver Qi Stagnation mix characteristics may has some relationship to ERa-rs9340799. ERP-rs3020444. Erβ-rsl 256030 genotype.