本文選題：圍絕經(jīng)期綜合征 + 肝郁　； 參考：《福建中醫(yī)藥大學(xué)》2016年博士論文

【摘要】：圍絕經(jīng)期綜合征(peirmenopausal period syndrome,PPS),是婦女在絕經(jīng)前后,雌激素水平下降,引起神經(jīng)內(nèi)分泌功能失調(diào),免疫功能下降和植物神經(jīng)系統(tǒng)功能紊亂的綜合征。肝郁是PPS重要病機(jī)。本研究運用證素辨證的方法對PPS肝郁及其兼雜特點展開研究,探討肝郁證的兼雜特征及其與植物神經(jīng)系統(tǒng)功能紊亂等常見癥狀之間的關(guān)系。同時從單胺類等神經(jīng)遞質(zhì)水平研究產(chǎn)生肝郁及其兼雜證的物質(zhì)基礎(chǔ),并從基因?qū)用娣治鰢^經(jīng)期綜合征肝郁及其兼雜特征的易感性,以深化對PPS肝郁的病機(jī)認(rèn)識,同時為PPS的肝郁的早期診斷及防治提供客觀的依據(jù)。第一部分圍絕經(jīng)期綜合征證素分布及肝郁兼雜特征與常見癥狀的相關(guān)性研究目的：分析PPS婦女的病位病性規(guī)律和肝郁的兼雜特征,探討PPS常見癥狀與肝郁病理及其兼雜特征的相關(guān)性。方法：收集PPS患者459例,采集相關(guān)臨床資料,以證素辨證的方法分析PPS的病位病性證素特征,肝郁兼雜特征,對PPS常見證素進(jìn)行聚類分析,分析肝郁及其兼雜與PPS常見癥狀的關(guān)系。結(jié)果：(1)PPS前六位常見癥狀依次為感覺異常(64.49%),失眠(59.48%),易激動(54.68%),眩暈(47.93%),骨關(guān)節(jié)痛、肌肉痛(46.19%),潮熱汗出(43.57%)(2)PPS病位涉及心、肝、脾、肺、腎、胞宮、胃、膽、大腸和膀胱。肝為最多72.55%(P0.01),其次為腎、脾和胞宮(p0.01)。(3)PPS實證病性涉及氣滯、痰、濕、血瘀、熱、寒。氣滯為最多達(dá)58.39%,以氣滯、痰、濕、血瘀為主(p0.01)(4)PPS虛證病性涉及陰虛、氣虛、血虛、陽虛、陽亢、精虧。其中以陰虛為最多69.72%(p0.01),其次為氣虛、血虛和陽虛(p0.01),再次為陽亢。(5)PPS常見病位病性證素聚類顯示氣滯、血瘀、痰和肝為一大類,氣虛、陽虛、血虛、陰虛、脾、腎、濕為一大類,其余病性病位為一大類。(6)PPS的常見癥狀中,肝郁組的眩暈發(fā)生率低于非肝郁組(p0.05 J,骨關(guān)節(jié)痛、肌肉痛發(fā)生率高于非肝郁組(p0.05),其他癥狀發(fā)生率無差別。(7)PPS肝郁兼雜特征：病位兼雜主要為腎、脾和胞宮；實證病性兼雜主要為痰、血瘀、濕、和熱；虛證病性兼雜主要為陰虛、氣虛、血虛、陽虛：(8)PPS肝郁兼雜特征對其常見癥狀的影響：肝郁病位兼腎者潮熱汗出的發(fā)生率高于病位不兼腎者(p0.05)；肝郁兼血瘀者骨關(guān)節(jié)痛肌肉痛的發(fā)生率顯著高于無兼血瘀者(p0.01),潮熱汗出、失眠的發(fā)生率高于無兼血瘀者(p0.05)；肝郁兼熱的抑郁發(fā)生率高于無兼熱者(p0.05)；肝郁兼氣虛者心悸的發(fā)生率顯著高于無兼氣虛者(p0.01),泌尿系癥狀發(fā)生率高于無兼氣虛者(p0.05)：肝郁兼陰虛者泌尿系癥狀發(fā)生率顯著高于無兼陰虛者(p0.01)；肝郁兼血虛者泌尿系癥狀發(fā)生率高于無兼血虛者(p0.05)結(jié)論：1.PPS是多個臟腑功能失調(diào)的結(jié)果,病性涉及寒熱虛實,其中主要病位在肝、腎、脾、胞宮：實證以氣滯、痰、濕、血瘀為主；虛證以陰虛、氣虛、血虛、陽虛為主。實證多與肝有關(guān),虛證多與腎、脾有關(guān)。2.PPS肝郁常兼腎、脾、胞宮的病理變化,也常兼痰、血瘀、濕、和熱之實證,和陰虛、氣虛、血虛、陽虛的虛證。3.PPS肝郁及其兼雜特征會影響PPS常見癥狀的表現(xiàn)形式。第二部分圍絕經(jīng)期綜合征肝郁及其兼雜特征的分子生物學(xué)基礎(chǔ)研究一、圍絕經(jīng)期綜合征肝郁與神經(jīng)遞質(zhì)的相關(guān)性研究目的：觀察PPS肝郁及其兼雜特征與神經(jīng)遞質(zhì)的關(guān)系,探討PPS肝郁及其兼雜特征的部分分子生物學(xué)基礎(chǔ)。方法：應(yīng)用ELISA等方法檢測189例PPS患者血液中的單胺類神經(jīng)遞質(zhì)(5-羥色胺5-HT,去甲腎上腺素NE,多巴胺DA)以及p內(nèi)啡肽p-EP。比較PPS肝郁組和非肝郁組神經(jīng)遞質(zhì)差異,比較肝郁不同兼雜神經(jīng)遞質(zhì)差異。結(jié)果：(1)肝郁組總膽紅素、直接膽紅素、間接膽紅素顯著高于非肝郁組(p0.01),肝郁組FSH高于非肝郁組(p0.01)(2)基于肝郁Logistic回歸中,進(jìn)入方程的自變量是直接膽紅素、谷氨酰轉(zhuǎn)肽酶和谷丙轉(zhuǎn)氨酶(p0.01)(3)肝郁組的DA和NE較非肝郁組為低(p0.05)(4)肝郁病位兼腎者DA和5-HT顯著低于單純肝郁者(p0.01)：肝郁兼痰者DA顯著低于無痰者(p0.01),5-HT低于無痰者(p0.05)；肝郁兼濕者5-HT顯著低于無濕者(p0.01)；肝郁兼熱者5-HT顯著低于無熱者(p0.01)：肝郁兼氣虛者5-HT顯著低于無氣虛者(p0.01)；肝郁兼血虛者DA和5-HT均顯著低于無血虛者(p0.01)；肝郁兼陰虛者DA和5-HT均低于無陰虛者(p0.05)結(jié)論：1.PPS患者DA和NE的降低可能是肝郁發(fā)生的分子生物學(xué)基礎(chǔ)。2.PPS單胺類神經(jīng)遞質(zhì)的變化與肝郁兼雜特點密切相關(guān)。3.總膽紅素、直接膽紅素、間接膽紅素可以做為PPS肝郁辨證的客觀依據(jù)之一二、圍絕經(jīng)期綜合征肝郁與雌激素受體基因多態(tài)性相關(guān)性研究且的：觀察PPS肝郁及其兼雜特征與ER基因型的關(guān)系,挖掘PPS肝郁及其兼雜特征的易感因素方法：應(yīng)用探針法檢測189例PPS患者血液中ERα [rs9340799 A/G]、ERβ[rs1256030 C/T,rs3020444 T/C]多態(tài)性。結(jié)果：(1)肝郁組的ERβ-rs3020444-TT頻率(85.93%)高于與非肝郁組(65.57%)(p0.01)其余基因型分布無差異。PPSERβ-rs3020444為TT型的患者發(fā)生肝郁證的相對危險度為3.208。(2)肝郁患者Erβ-rs3020444 和 Erβ-rs 1256030的TT/CC頻率高于非肝郁者(p0.05),肝郁患者Erβ-rs3020444 和 ERβ-rs9340799的TT/AG勺頻率高于非肝郁者(p0.05),TC/AG和CC/AG的頻率低于非肝郁者(p0.05)(3)肝郁兼濕、兼痰ERβ-rs3020444基因型分布分別與無濕,無痰者有差異(p0.05)肝郁兼熱、兼氣虛ERβ-rs1256030基因型分布分別與無熱、無氣虛者有差異(p0.05),肝郁兼濕、兼氣虛、兼血虛、兼陽虛ERa-rs9340799基因型分布分別與無濕、無氣虛、無血虛、無陽虛有差異(p0.05)結(jié)論：1. ERp-rs3020444-TT型可能是PPS肝郁證的遺傳易感基礎(chǔ)之一2.PPS肝郁兼雜的易感性與ERα-rs9340799、ERp-rs3020444、Erp-rs1256030基因型有關(guān)。
[Abstract]:Perimenopausal syndrome (peirmenopausal period syndrome, PPS) is a syndrome of the decrease of estrogen level in the premenopause, the dysfunction of neuroendocrine function, the decline of immune function and the dysfunction of the autonomic nervous system. The liver depression is an important pathogenesis of PPS. The method of syndrome differentiation for the use of syndrome elements is used to show the characteristics of PPS liver depression and its concurrently miscellaneous characteristics. The relationship between the characteristics of the liver depression syndrome and the common symptoms such as the dysfunction of the autonomic nervous system and other common symptoms was studied. At the same time, the physical basis of liver depression and its facultative syndrome was produced from the level of monoamine neurotransmitters, and the susceptibility of the liver depression and its facultative characteristics of perimenopausal syndrome was analyzed from the gene level, so as to deepen the PPS liver. It provides an objective basis for the early diagnosis and prevention of the liver depression of PPS. The first part of the perimenopause syndrome distribution and the correlation between the characteristics of liver depression and miscellaneous and common symptoms and the common symptoms of PPS women: analysis of the regularity of the disease and the facultative syndrome of the liver depression, and discuss the common symptoms of PPS and the pathology of the liver depression and the pathology of the liver depression. Methods: 459 cases of PPS patients were collected and related clinical data were collected. The characteristics of the syndrome factor of PPS's disease, liver depression and miscellaneous characteristics were analyzed by the method of syndrome differentiation and syndrome differentiation, and the common symptoms of PPS were analyzed by cluster analysis. The results were as follows: (1) the first six common symptoms of PPS were the sense of feeling. Abnormality (64.49%), insomnia (59.48%), irritability (54.68%), vertigo (47.93%), bone and joint pain, muscle pain (46.19%), hot moisture and sweat (43.57%) (2) PPS disease involved heart, liver, spleen, lung, kidney, uterus, stomach, bile, large intestine and bladder. The liver was 72.55% (P0.01), followed by kidney, spleen and the uterus (3). (3) PPS empirical disease related to qi stagnation, phlegm, dampness, blood stasis, heat, cold. Qi stagnation was up to 58.39%, with qi stagnation, phlegm, dampness and blood stasis (P0.01) (4) PPS deficiency syndrome related to yin deficiency, Qi deficiency, deficiency of blood, Yang deficiency, yang hyperactivity, and fine deficiency. Among them, yin deficiency was 69.72% (P0.01), followed by qi deficiency, blood deficiency and yang deficiency (P0.01), and yang hyperactivity. (5) the cluster of common diseases in PPS showed qi stagnation, blood stasis, phlegm and liver as a major category. Qi deficiency, deficiency of Yang, deficiency of blood, yin deficiency, spleen, kidney and dampness are a major category. (6) in the common symptoms of PPS, the incidence of vertigo in the liver depression group is lower than that of the non stagnation group (P0.05 J, bone and joint pain, and the incidence of muscle pain is higher than that of the non stagnation group (P0.05), and the incidence of his symptoms is not different. (7) PPS liver depression and miscellaneous features: the position and miscellaneous main disorders are mainly the diseased position and heterozygosity. The kidney, spleen and the cyst of the uterus were mainly phlegm, blood stasis, wet, and heat. Deficiency syndrome and miscellaneous mainly were Yin deficiency, Qi deficiency, blood deficiency and yang deficiency: (8) the effect of PPS liver depression and miscellaneous characteristics on its common symptoms: the incidence of hot sweat and sweat out of the liver depression and kidney people was higher than that of the patients with no kidney (P0.05), and the bone and joint pain muscle pain in the stagnation and blood stasis patients with liver depression and blood stasis. The incidence of fever and perspiration was higher than those with no blood stasis (P0.01). The incidence of insomnia was higher than that of non blood stasis (P0.05); the incidence of depression in liver depression and heat was higher than that of non heat (P0.05); the incidence of palpitation in the liver depression and Qi deficiency was significantly higher than that of the non Qi deficiency (P0.01), and the incidence of urinary system symptoms was higher than that of the non Qi deficiency (P0.05): liver depression. The incidence of urinary system symptoms in patients with Yin deficiency was significantly higher than that of non Yin deficiency (P0.01). The incidence of urinary tract symptoms in patients with liver depression and blood deficiency was higher than that of non facultative deficiency (P0.05) conclusion: 1.PPS is the result of multiple viscera dysfunction, and the disease involves the deficiency of cold and heat, among which the main diseases are in the liver, kidney, spleen, and uterus: Qi stagnation, phlegm, dampness and blood stasis Deficiency syndrome is mainly with Yin deficiency, Qi deficiency, blood deficiency and yang deficiency. The evidence is mostly related to the liver, the deficiency syndrome is more with the kidney and the kidney, the pathological changes of the.2.PPS liver depression and the kidney, the spleen and the cyst of the uterus are also often concurrent with the phlegm, blood stasis, damp, and heat, and the deficiency of Yin, Qi deficiency, blood deficiency and yang deficiency syndrome of.3.PPS liver depression and its facultative characteristics will affect the manifestations of the common symptoms of PPS. Second Study on the relationship between liver depression and neurotransmitters in perimenopausal syndrome: Study on the correlation between liver depression and neurotransmitters in perimenopausal syndrome. Objective: To observe the relationship between PPS liver depression and its facultative characteristics and neurotransmitters, and to explore the molecular basis of PPS liver depression and its facultative characteristics. Methods: the application of ELISA and so on. The monoamine neurotransmitters (5- serotonin 5-HT, norepinephrine NE, dopamine DA) and P endorphin p-EP. were measured in 189 patients with PPS, and the difference in neurotransmitters between the liver depression and the non stagnation group was compared with the P endorphin p-EP., and the difference between the liver depression and the heterozygous neurotransmitters was compared. Results: (1) the total bilirubin, direct bilirubin and indirect bilirubin were significantly higher in the liver depression group. In the non stagnation group (P0.01), the FSH in the liver depression group was higher than that of the non stagnation group (P0.01) (2) based on the liver depression Logistic regression, the independent variables entered the equation were direct bilirubin, the DA and NE in the group of glutamyl transaminase and alanine transaminase (P0.01) (3) liver depression were lower than those of the non stagnation group (P0.05) (4) of the liver depression and kidney, DA and 5-HT were significantly lower than those of the simple liver depression (P0.01). Liver depression and phlegm DA were significantly lower than those without phlegm (P0.01), 5-HT was lower than non phlegm (P0.05), 5-HT of liver depression and dampness was significantly lower than that without damp (P0.01); 5-HT was significantly lower than non heat (P0.01) in liver depression and hot people (P0.01): Liver depression and Qi deficiency patients were significantly lower than those without Qi deficiency (P0.01); DA and 5-HT were significantly lower than those without blood deficiency; liver depression and deficiency of blood were significantly lower than those without blood deficiency; liver depression and deficiency of blood were significantly lower than those without blood deficiency; liver depression and deficiency of liver Qi were significantly lower than those without blood deficiency; liver depression and deficiency of liver Qi were significantly lower than those of non blood deficiency patients. Both DA and 5-HT were lower than those without Yin deficiency (P0.05). The decrease of DA and NE in 1.PPS patients may be the molecular biological basis of liver depression, the changes of monoamine neurotransmitters of.2.PPS and the characteristics of liver depression and heterozygosity closely related to.3. total bilirubin, direct bilirubin and indirect bilirubin can be one of the objective basis for the syndrome differentiation of PPS liver depression. Two, the correlation between the liver depression of perimenopausal syndrome and the polymorphism of estrogen receptor gene: the relationship between PPS liver depression and its facultative characteristics and ER genotypes was observed, and the susceptibility to PPS liver depression and its facultative characteristics was explored. The probe method was used to detect ER alpha [rs9340799 A/G], ER beta [rs1256030 C/T, rs3020444 T/ in the blood of 189 patients with PPS. The results were as follows: (1) the frequency of ER beta -rs3020444-TT in the liver depression group (85.93%) was higher than that in the non stagnation group (65.57%) (65.57%) (65.57%) (P0.01), and the relative risk of.PPSER beta -rs3020444 was TT type, the frequency of Er beta -rs3020444 and Er beta -rs 1256030 in the patients with 3.208. (2) liver depression was higher than that of non depression patients. The frequency of the TT/AG spoon of Er beta -rs3020444 and ER beta -rs9340799 in patients with liver depression was higher than that of non Stagnation (P0.05). The frequency of TC/AG and CC/AG was lower than that of non Stagnation (P0.05) (P0.05) (3) liver depression and humid, and the distribution of ER beta -rs3020444 genotypes in phlegm was different from that of no wet, no phlegm (P0.05) liver depression and heat. Qi deficiency (P0.05), liver depression and damp, Qi deficiency, concurrent blood deficiency, and yang deficiency ERa-rs9340799 genotype distribution respectively and no wet, no Qi deficiency, no blood deficiency, no difference between Yang deficiency (P0.05) conclusion: the 1. ERp-rs3020444-TT type may be the genetic susceptibility basis of PPS liver depression, one 2.PPS liver depression and miscellaneous susceptibility and ER alpha -rs9340799, ERp-rs3020444, Er. The genotype of p-rs1256030 is related.
【學(xué)位授予單位】：福建中醫(yī)藥大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R277.7

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5 林吟，

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