围绝经期肥胖痰、郁证素兼杂特征与体脂分布及脂肪因子表达关系的研究

The research group has found in preliminary study that Phlegm closely associated with visceral obesity ，Liver-qi Stagnation is the main pathogenesis among perimenopausal women. "Liver-qi Stagnation produces phlegm" is the pathological mechanism of body fat redistribution from periphery to center during perimenopause.Currently the basic study of TCM mixed relation between phlegm syndrome and Liver-qi Stagnation syndrome and body fat redistribution and its biological basis is absent.So basing on the early studies,this project is intended to set perimenopausal obese women as objects and complete the tasks as following:(1) Applying the syndrome elements differentiation to analyze the characteristics of qi and phlegm syndrome, the primary and secondary and the mixed relationship between them. (2) Using CT / DEXA to quantitatively determinate the body fat content in viscus and its distribution.(3)Using the technologies such as qPCR,westenblot and ELISA to study the differences of expression of estrogen receptor mRNA, protein, fat factor and the relationship between them. The purpose of this study is that: basing on the part theory of " Liver-qi Stagnation produces phlegm", the relationship of body fat distribution and syndrome elements would be investigated , the biological basis of qi stagnation and phlegm obstruction would be revealed on mRNA, protein levels. Then the scientific connotation of the relation between body fluid and qi in pathogenesis of Liver-qi Stagnation and phlegm obstruction would be enriched, and the basis of early diagnosis prevention and intervention for perimenopausal obesity would be provided.

课题组前期研究发现中心性肥胖与"痰"密切相关，围绝经期女性以"肝郁"为主要病机且肥胖发病率较高，因而认为肝郁痰阻是女性围绝经期因性激素水平变化出现体脂由均匀性转为中心性分布的中医病理基础，痰、郁证素的兼杂决定了体脂分布。为了探讨围绝经期肥胖证候特征、体脂分布及其分子生物学机制，本项目拟在前期研究基础上，以围绝经期肥胖女性为对象（1）以证素辨证法分析痰、郁证素分布特征及标本、兼杂关系（2）应用CT/DEXA定位定量测定内脏体脂分布和含量（3）以qPCR，westenblot,ELISA技术，研究雌激素受体mRNA、蛋白及脂肪因子表达差异。本研究目的在于：探讨围绝经期肥胖痰、郁异常的证候学基础及与体脂分布关系，同时也从mRNA、蛋白水平，初步揭示导致肥胖的分子生物学机制，丰富中医学气津关系之肝郁痰阻病机的科学内涵，为围绝经期肥胖早期诊断、治疗提供依据。

本课题通过对围绝经期肥胖和围绝经前期肥胖痰证肝郁、非肝郁以及健康对照组的采集，探讨分析围绝经期肥胖的肝郁、痰证的证素兼杂与体脂分布的关系、雌激素、雌激素受体mRNA、蛋白以及相关脂肪因子的关系。采集身高、体重、腰围等以及体脂分布测定；检验理化指标；ELISA检测雌激素和脂肪因子含量；Western blotting法检测ERα与ERβ的蛋白表达；RT-PCR法检测ERα与ERβ的基因数据表达。结果显示：围绝经期肥胖主要病位证素为脾、肝、肾，病性证素为痰、气滞、湿、血瘀、阳虚、气虚、阴虚、血虚；围绝经期肥胖痰证病位兼杂为肝、肾、脾，病性兼杂为湿、热、气滞、阴虚、阳虚、气虚、血虚;围绝经期肥胖痰证下肝郁证素积分均高于围绝经期肥胖痰证下的非肝郁组。围绝经期肥胖的以中心性为特点，其较育龄期妇女腹部更易产生脂肪异位沉积。围绝经期肥胖兼杂不同证素对血脂组分的影响各不相同；围绝经期肥胖痰证下肝郁证素兼杂中，胞宫者的脂联素含量高于非胞宫者，血虚者的内脂素含量高于非血虚者，脾者瘦素含量高于非脾者；肾者瘦素含量高于非肾者，阳虚者瘦素含量高于非阳虚者，血虚者瘦素含量高于非血虚者，胞宫者瘦素含量低于非胞者。围绝经期肥胖痰证肝郁的ERα的蛋白、mRNA表达高，围绝经期肥胖痰证肝郁的ERβ的蛋白、mRNA表达最低，围绝经期肥胖痰证下肝郁ERα/ERβ的蛋白、mRNA比值表达最高。结论：围绝经期肥胖妇女以痰证肝郁为病理特点，以中心性肥胖为特点；瘦素在围绝经期肥胖痰证肝郁表达差异性显著，其于脾、肾、阳虚、血虚证素兼杂相关，而雌激素、脂联素、网膜素、内脂素不完全相关；ERα、ERβ的蛋白、mRNA表达与肝郁证素相关，该数据认为血液循环中ERα和ERα/ERβ比率不能作为肥胖相关研究差异性指标。本研究为中医证素、脂肪因子、雌激素受体作为临床诊断围绝经期肥胖痰证肝郁提供了客观化的生物测量学依据。