证的形成是多因素作用的结果。本课题组前期研究表明，肝郁是围绝经期综合征（PPS）的主要病机，并贯穿于疾病的整个过程，但是，PPS肝郁证的形成机制及其与自然衰老、情志刺激的关系尚未阐明。本课题（1）采用自然衰老PPS大鼠模型及自然衰老+慢性束缚所致的PPS肝郁证大鼠模型，以柴胡疏肝散（CHSGS）验证，从动物行为、HPA轴及HPO轴的不同层面激素水平及超微结构的改变，探讨PPS肝郁证的形成与自然衰老、情志刺激的关系。（2）从大鼠海马Ras/Raf/MEK/ERK信号通路相关基因、蛋白的表达变化，分析PPS肝郁证形成的分子生物学机制及CHSGS的干预作用；（3）建立体外海马神经元细胞体系，采用定量PCR技术检测CHSGS、CHSGS +抑制剂处理后Ras/Raf/MEK/ERK通路相关基因表达变化，进一步体外验证。本研究将进一步丰富PPS肝郁证的病机理论，为PPS的预防及从肝论治提供实验依据。

The formation of Syndrome results from multiple factors. Our previous studies showed that, liver-qi stagnation is the major pathogenesis of perimenopausal period syndrome (PPS), and runs through the whole process of disease. But the relationship between formation of PPS liver-qi stagnation syndrome and natural aging, emotional stimuli remains unclear. First of all, We use the model of natural aging PPS rats, natural aging rat combining with bound feeding, The rats of treated groups were intragastric administered with herbal formula Chaihu-shugan-san (CHSGS) for 3 weeks.We observe the changes of hormone levels and ultrastructure of HPA and HPO axis, and animal behavior, analyse the relationship between formation of liver-qi stagnation syndrome in perimenopausal period syndrome and the natural aging, emotional stimuli. Secondly, Based on the changes of related genes and protein in rat hippocampus Ras/Raf/MEK/ERK signaling pathway, we explore the molecular mechanism of formation of liver-qi stagnation syndrome in perimenopausal period syndrome. Thirdly,We establish the cell system of hippocampal neurons in vitro, use the real-time pcr technique to detect the genes expression of Ras/Raf/MEK/ERK pathway after treated with CHSGS or CHSGS combine with specific inhibitors of pathway.This study is expected to further enrich the pathogenesis theory of liver-qi stagnation syndrome,to provide the experimental basis for theory of PPS prevention and treatment from liver.