【作者】 徐琬梨；

【导师】 刘家义；

【作者基本信息】 山东中医药大学 ， 中医诊断学， 2013， 博士

【摘要】 目的：1.通过对有明确证型且有确切治疗效果的多囊卵巢综合征（polycystic ovariansyndrome,PCOS）临床试验及病历报告文献进行统计学分析，研究能够取得满意疗效的PCOS常见证素及证素组合规律，把握疾病病机及演变规律，为临床治疗提供依据。2.通过检测多囊卵巢综合征痰湿证患者卵巢黄素化颗粒细胞胰岛素受体底物2（insulin receptor substrate-2,IRS-2）蛋白表达及酪氨酸磷酸化程度，基于证素辨证学，在前期研究的基础上继续探讨PCOS痰湿证卵巢局部胰岛素抵抗的分子机制及生殖功能障碍的发病机理。方法：1.用计算机检索与手工查阅相结合的方法检索具有明确证候分型并且有确切治疗效果（经连续3个月或3个月经周期治疗后以怀孕或正常排卵）临床试验及病历报告的文献。编写《多囊卵巢综合征中医证候文献整理规范》，用朱文锋教授研制的“证素辨证”方法，将证名分解为辨证的基本要素即证素，将原始资料数据量化后录入计算机，建立PCOS中医证候文献研究数据库，采用SPSS16.0统计软件进行统计描述。2.收集行体外受精-胚胎移植（IVF-ET）治疗的PCOS患者60例（痰湿证组30例，非痰湿证组30例）和输卵管性不孕症患者30例（对照组）超促排卵后的卵巢黄素化颗粒细胞，采用化学发光法检测3组空腹血清胰岛素（fasting insulin,FIN）水平；采用葡萄糖氧化酶法测定3组空腹血糖（fasting plasma glucose,FPG）水平；利用稳态模型（homeostasis model assessment,HOMA）计算胰岛素抵抗指数（HOMA-IR）；采用免疫印迹法（Western blot）检测3组卵巢黄素化颗粒细胞IRS-2蛋白表达及酪氨酸磷酸化程度。结果：1.文献研究结果：病位证素5个，其中肾出现频率最高为74.03%；病性证素9个，虚性证素中阳虚出现频率最高为67.53%，实性证素中痰（湿、浊）出现频率最高为71.43%；关于病位证素的组合形式中2病位组合（44.16%）与3病位组合（33.77%）所占构成比较高，关于病性证素的组合形式中虚实夹杂所占构成比最高为72.73%。2.各组患者黄素化颗粒细胞IRS-2蛋白表达比较：PCOS痰湿证组与对照组比较，颗粒细胞IRS-2蛋白的表达水平明显低于对照组，差异有统计学意义（P<0.01）；PCOS非痰湿证组与对照组比较，颗粒细胞IRS-2蛋白的表达水平明显低于对照组，差异有统计学意义（P<0.01）；PCOS痰湿证组与非痰湿证组比较，前者IRS-2蛋白的表达水平低于后者，差异有统计学意义（P<0.05）。3.各组患者黄素化颗粒细胞IRS-2酪氨酸磷酸化程度比较：PCOS痰湿证组与对照组比较，颗粒细胞IRS-2酪氨酸磷酸化程度低于对照组，差异有统计学意义（P<0.01）；PCOS非痰湿证组与对照组比较，颗粒细胞IRS-2酪氨酸磷酸化程度低于对照组，差异有统计学意义（P<0.01）；PCOS痰湿证组与非痰湿证组比较，前者IRS-2酪氨酸磷酸化程度低于后者，差异有统计学意义（P<0.05）。结论：1.经中医或中西医结合治疗有确切良好疗效的多囊卵巢综合征的主要病机为阳虚和痰湿内盛，所涉及五脏病位主要为肾，病性以虚实夹杂为主。2. PCOS痰湿证患者卵巢局部存在胰岛素抵抗，其原因可能与IRS-2蛋白表达及酪氨酸磷酸化异常有关。3.痰湿为致病邪气中可以导致卵巢局部胰岛素受体后信号转导障碍的重要致病因素，为“痰壅胞宫”是PCOS-IR的重要病机提供支持。更多还原

【Abstract】 Objective:1. To study the distribution regularity of syndrome essential elements of Polycysticovarian syndrome based on literature data.2. To detecte the degree of tyrosine phosphorylation and protein expression of insulinreceptor substrate2in ovarian luteinizing granulose cells from the patients of polycysticovary syndrome with Phlegm-dampness, and discuss the molecular mechanism of insulinresistance and the pathogenesis of reproductive dysfunction in the patients of polycysticovary syndrome with Phlegm-dampness.Methods:1. Literatures about PCOS collected from CBM,CNKI and TCM, the criterion and thedatabase of TCM syndrome of PCOS were setup, SPSS16.0for windows software wasadopted for statistical description.2. Select60PCOS patients under treatment of vitro fertilisation and embryotransplantation （IVF-ET）（30cases in phlegm-dampness group,and30cases innon-phlegm-dampness group） and30cases oviduct infertility patients （control group）promote ovarian syndrome after superovulation granular cell. Use of steady-state model（homeostasis model assessment, HOMA） to calculate insulin resistance index（HOMA-IR）; By immune imprinting（Western blot）method to detect degree of IRS-2syndrome protein expression and tyrosine phosphorylation of ovarian granulosa cell in thethree groups.Results:1. In all the syndrome factors, there was5disease location ones and9disease nature ones. In the5disease location syndrome factors, kidney had the highest frequency74.03%.The main pathological deficiency factors of PCOS was yang deficiency with the frequency67.53%. The main pathological overabundance factors of PCOS was dampness with thefrequency67.53%. In the combination of essential elements of syndrome, the combinationof two（44.16%）and three（33.77%） elements have higher frequency. And the othercombination was relatively few. The combination of essential elements of syndrome withdeficiency factors and overabundance factors had the highest frequency72.73%.2.Comparison of the protein expression of granular cell IRS-2in each group:Compared with control group, the protein expression of IRS-2in two groups of PCOSpatients were significantly higher （P <0.01）, and PCOS phlegm-dampness group wassignificantly lower than non-phlegm-dampness group （P <0.05）.3. comparison of degree of IRS-2tyrosine phosphorylation in granular cell: Comparedwith control group, IRS-2tyrosine in two groups of PCOS were significantly lower （P <0.01）, and PCOS phlegm-dampness group was significantly lower than non-phlegm-dampness group （P <0.01）.Conclusions:1.So the main syndrome target point viscera is the kidney. The main pathologicalfactors of PCOS was dampness and they often combine each other.2.Local area of ovarian in patients of phlegm-dampness PCOS group has insulinresistance, its reason may related with anomalies of protein expression of IRS-2andtyrosine phosphorylation，provide objective basis for the diagnosis of PCOS phlegm-dampness syndrome.3.“Tan Shi”is the main important aspects in format the insulin resistance of PCOSphlegm-dampness.更多还原