经前烦躁障碍（PMDD）肝气逆/郁病证大鼠模型鉴定与标准化

Premenstrual dysphoric disorder (PMDD) is a severe type of premenstrual syndrome, and has been paid special attention by the medical profession at home and abroad. International recent studies have shown: PMDD rat models have aggressiveness and depression subtypes, but failed to identify separately. Our previous study showed that: Liver-Qi Invasion (LQI) and Liver-Qi Depression (LQD) are two main syndromes belongs to PMDD. Rat model had simulated the clinical manifestations of the disease with syndrome, but not yet identified the key clinical features that symptoms presented during premenstrual period (equivalent to non-receptive phase of rat estrous cycle) and disappeared after menstruation (equivalent to receptive phase of rat estrous cycle). The project hold this critical issue tightly, and strive to achieve a breakthrough to establish the standard of rat model modeling, evaluation and application. To achieve this goal, we prepare to conduct the behavior phenotype identification of during receptive and non-receptive phases of rat model of PMDD with LQI and LQD establishing the rat model in line with the key clinical features of the disease with syndrome; we prepare to explore the important index change in brain and peripheral blood of rat model to verify its stability and reliability; we prepare to research the modeling and evaluation criteria, investigate and confirm the model disease with syndrome information reliability, validity and responsiveness to establish model technical standards. All of the works mentioned above will provide the standard rat model for the research of GanZangXiang and the Chinese medicine drug development, provide the standard disease with syndrome rat model for the international frontier research in this field.

经前烦躁障碍（PMDD）是经前期综合征的严重类型，国内外医学界格外关注。国际近年研究显示：PMDD大鼠具有愤怒攻击和抑郁退缩两类亚型表现，但未能鉴别分开。我们前期研究表明：肝气逆/郁是PMDD两个主要证候；PMDD肝气逆/郁病证大鼠模型模拟出该病证临床表现，但尚未鉴定出“经前（大鼠非接受期）呈现症状，经行（接受期）症状消失”这一关键临床特征。本项目紧扣这一关键问题，力求取得突破，进而建立该病证大鼠造模与评价及应用标准。为实现这一目标，进行PMDD肝气逆/郁病证模型大鼠动情非接受与接受期行为表现的鉴定研究，建立起符合该病证关键临床特征大鼠模型；探查该病证模型大鼠脑内及外周血重要指标变化，佐证模型稳定可靠；研究模型造模与评价标准，考察并确认模型病证信息的信度、效度和反应度，建立起模型技术标准。为中医肝脏象科研和中药新药研发，提供急需标准模型；为该领域国际前沿研究，提供具有标准的病证结合模型。

经前烦躁障碍（PMDD）是经前期综合征的严重类型，国内外医学界格外关注。国际近年研究显示：PMDD大鼠具有愤怒攻击和抑郁退缩两类亚型表现，但未能鉴别分开。我们前期研究表明：肝气逆/郁是PMDD两个主要证候；PMDD肝气逆/郁病证大鼠模型模拟出该病证临床表现，但尚未鉴定出“经前（大鼠非接受期）呈现症状，经行（接受期）症状消失”这一关键临床特征。本项目紧扣这一关键问题，力求取得突破，进而建立该病证大鼠造模与评价及应用标准。经过四年潜心研究，所得结果显示：针对居住入侵法制备的PMDD肝气逆证大鼠模型，我们采用旷场实验、高架十字迷宫实验以及攻击行为学实验等行为学检测手段进行如下实验：PMDD肝气逆证大鼠动情周期依赖性检测，PMDD肝气逆证大鼠卵巢切除反证实验，PMDD肝气逆证大鼠卵巢切除后激素诱导实验，发现该模型确能模拟PMDD肝气逆证“烦躁易怒”的主要症状；针对强迫游泳法制备的PMDD肝气郁证大鼠模型，采用FST、EPM测试，其中接受期1次、非接受期两次，结果显示，该方法确能模拟出PMDD肝气郁证临床患者“抑郁寡欢”的主要症状。上述两种模型均能表现PMDD肝气逆、郁两证首要表现“经前症状出现，经后消失或减弱”。其次，本项目通过检测血清及关键脑区激素、神经递质，以及关键基因GABAARα4亚基表达，发现，与PMDD肝气逆、郁两证相关的关键指标是E2、P、5-HT、NE、GABA,以及GABAARα4亚基的异常表达，主要对证干预方药白香丹胶囊和舒郁胶囊均能很好的纠正上述关键指标的异常表达。通过上述研究建立起PMDD肝气逆、郁两证造模与评价技术标准。这为中医肝脏象科研和中药新药研发，提供急需标准模型；为该领域国际前沿研究，提供具有标准的病证结合模型。