围绝经期综合征肝郁证兼杂特征及其分子生物学基础研究

发布时间：2018-05-25 17:35

本文选题：围绝经期综合征 + 肝郁　；参考：《福建中医药大学》2016年博士论文

【摘要】：围绝经期综合征(peirmenopausal period syndrome,PPS),是妇女在绝经前后,雌激素水平下降,引起神经内分泌功能失调,免疫功能下降和植物神经系统功能紊乱的综合征。肝郁是PPS重要病机。本研究运用证素辨证的方法对PPS肝郁及其兼杂特点展开研究,探讨肝郁证的兼杂特征及其与植物神经系统功能紊乱等常见症状之间的关系。同时从单胺类等神经递质水平研究产生肝郁及其兼杂证的物质基础,并从基因层面分析围绝经期综合征肝郁及其兼杂特征的易感性,以深化对PPS肝郁的病机认识,同时为PPS的肝郁的早期诊断及防治提供客观的依据。第一部分围绝经期综合征证素分布及肝郁兼杂特征与常见症状的相关性研究目的：分析PPS妇女的病位病性规律和肝郁的兼杂特征,探讨PPS常见症状与肝郁病理及其兼杂特征的相关性。方法：收集PPS患者459例,采集相关临床资料,以证素辨证的方法分析PPS的病位病性证素特征,肝郁兼杂特征,对PPS常见证素进行聚类分析,分析肝郁及其兼杂与PPS常见症状的关系。结果：(1)PPS前六位常见症状依次为感觉异常(64.49%),失眠(59.48%),易激动(54.68%),眩晕(47.93%),骨关节痛、肌肉痛(46.19%),潮热汗出(43.57%)(2)PPS病位涉及心、肝、脾、肺、肾、胞宫、胃、胆、大肠和膀胱。肝为最多72.55%(P0.01),其次为肾、脾和胞宫(p0.01)。(3)PPS实证病性涉及气滞、痰、湿、血瘀、热、寒。气滞为最多达58.39%,以气滞、痰、湿、血瘀为主(p0.01)(4)PPS虚证病性涉及阴虚、气虚、血虚、阳虚、阳亢、精亏。其中以阴虚为最多69.72%(p0.01),其次为气虚、血虚和阳虚(p0.01),再次为阳亢。(5)PPS常见病位病性证素聚类显示气滞、血瘀、痰和肝为一大类,气虚、阳虚、血虚、阴虚、脾、肾、湿为一大类,其余病性病位为一大类。(6)PPS的常见症状中,肝郁组的眩晕发生率低于非肝郁组(p0.05 J,骨关节痛、肌肉痛发生率高于非肝郁组(p0.05),其他症状发生率无差别。(7)PPS肝郁兼杂特征：病位兼杂主要为肾、脾和胞宫；实证病性兼杂主要为痰、血瘀、湿、和热；虚证病性兼杂主要为阴虚、气虚、血虚、阳虚：(8)PPS肝郁兼杂特征对其常见症状的影响：肝郁病位兼肾者潮热汗出的发生率高于病位不兼肾者(p0.05)；肝郁兼血瘀者骨关节痛肌肉痛的发生率显著高于无兼血瘀者(p0.01),潮热汗出、失眠的发生率高于无兼血瘀者(p0.05)；肝郁兼热的抑郁发生率高于无兼热者(p0.05)；肝郁兼气虚者心悸的发生率显著高于无兼气虚者(p0.01),泌尿系症状发生率高于无兼气虚者(p0.05)：肝郁兼阴虚者泌尿系症状发生率显著高于无兼阴虚者(p0.01)；肝郁兼血虚者泌尿系症状发生率高于无兼血虚者(p0.05)结论：1.PPS是多个脏腑功能失调的结果,病性涉及寒热虚实,其中主要病位在肝、肾、脾、胞宫：实证以气滞、痰、湿、血瘀为主；虚证以阴虚、气虚、血虚、阳虚为主。实证多与肝有关,虚证多与肾、脾有关。2.PPS肝郁常兼肾、脾、胞宫的病理变化,也常兼痰、血瘀、湿、和热之实证,和阴虚、气虚、血虚、阳虚的虚证。3.PPS肝郁及其兼杂特征会影响PPS常见症状的表现形式。第二部分围绝经期综合征肝郁及其兼杂特征的分子生物学基础研究一、围绝经期综合征肝郁与神经递质的相关性研究目的：观察PPS肝郁及其兼杂特征与神经递质的关系,探讨PPS肝郁及其兼杂特征的部分分子生物学基础。方法：应用ELISA等方法检测189例PPS患者血液中的单胺类神经递质(5-羟色胺5-HT,去甲肾上腺素NE,多巴胺DA)以及p内啡肽p-EP。比较PPS肝郁组和非肝郁组神经递质差异,比较肝郁不同兼杂神经递质差异。结果：(1)肝郁组总胆红素、直接胆红素、间接胆红素显著高于非肝郁组(p0.01),肝郁组FSH高于非肝郁组(p0.01)(2)基于肝郁Logistic回归中,进入方程的自变量是直接胆红素、谷氨酰转肽酶和谷丙转氨酶(p0.01)(3)肝郁组的DA和NE较非肝郁组为低(p0.05)(4)肝郁病位兼肾者DA和5-HT显著低于单纯肝郁者(p0.01)：肝郁兼痰者DA显著低于无痰者(p0.01),5-HT低于无痰者(p0.05)；肝郁兼湿者5-HT显著低于无湿者(p0.01)；肝郁兼热者5-HT显著低于无热者(p0.01)：肝郁兼气虚者5-HT显著低于无气虚者(p0.01)；肝郁兼血虚者DA和5-HT均显著低于无血虚者(p0.01)；肝郁兼阴虚者DA和5-HT均低于无阴虚者(p0.05)结论：1.PPS患者DA和NE的降低可能是肝郁发生的分子生物学基础。2.PPS单胺类神经递质的变化与肝郁兼杂特点密切相关。3.总胆红素、直接胆红素、间接胆红素可以做为PPS肝郁辨证的客观依据之一二、围绝经期综合征肝郁与雌激素受体基因多态性相关性研究且的：观察PPS肝郁及其兼杂特征与ER基因型的关系,挖掘PPS肝郁及其兼杂特征的易感因素方法：应用探针法检测189例PPS患者血液中ERα [rs9340799 A/G]、ERβ[rs1256030 C/T,rs3020444 T/C]多态性。结果：(1)肝郁组的ERβ-rs3020444-TT频率(85.93%)高于与非肝郁组(65.57%)(p0.01)其余基因型分布无差异。PPSERβ-rs3020444为TT型的患者发生肝郁证的相对危险度为3.208。(2)肝郁患者Erβ-rs3020444 和 Erβ-rs 1256030的TT/CC频率高于非肝郁者(p0.05),肝郁患者Erβ-rs3020444 和 ERβ-rs9340799的TT/AG勺频率高于非肝郁者(p0.05),TC/AG和CC/AG的频率低于非肝郁者(p0.05)(3)肝郁兼湿、兼痰ERβ-rs3020444基因型分布分别与无湿,无痰者有差异(p0.05)肝郁兼热、兼气虚ERβ-rs1256030基因型分布分别与无热、无气虚者有差异(p0.05),肝郁兼湿、兼气虚、兼血虚、兼阳虚ERa-rs9340799基因型分布分别与无湿、无气虚、无血虚、无阳虚有差异(p0.05)结论：1. ERp-rs3020444-TT型可能是PPS肝郁证的遗传易感基础之一2.PPS肝郁兼杂的易感性与ERα-rs9340799、ERp-rs3020444、Erp-rs1256030基因型有关。
[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.
【学位授予单位】：福建中医药大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R277.7

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