滋阴泻火方调控下丘脑KDNy神经元PcG/TrxG 复合体表观遗传效应治疗双酚A诱发性早熟的机制探讨

特发性性早熟（ICPP）发病与先天禀赋，营养状态，环境内分泌干扰物（EEDs）等有关，标志是下丘脑脉冲性GnRH释放提前出现。双酚A（BPA）是最常见的EEDs，对下丘脑-垂体-性腺轴相关基因表达有表观遗传调控影响。BPA有类性激素这一“纯阳"活性，过度暴露可使患儿肾气过培，肾阴阳失衡，相火偏旺，导致ICPP，但机制不明。KDNy神经元是调节GnRH的关键通路，PcG/TrxG复合体介导的组蛋白修饰可调节它的功能，在青春期启动中有重要作用。BPA是否可通过此调节KDNy神经元导致"肾"阴阳失衡诱发ICPP尚不明确。既往研究显示：滋阴泻火中药可有效治疗性早熟。本课题采用BPA诱发大鼠CPP模型，探讨KDNy神经元PcG/TrxG复合体介导的组蛋白修饰在BPA诱发"肾"阴阳失衡导致ICPP中的作用及滋阴泻火中药通过相关表观遗传效应多靶点治疗ICPP的机制。

Idiopathic precocious puberty (ICPP) is closely related with parental heredity, nutritional status, environmental endocrine disruptors (EEDs), etc., marked by the advancement of pulsatile hypothalamic GnRH release. Bisphenol A (BPA) having an epigenetic effect on hypothalamus-pituitary-gonad axis relevant genes expression is the most common EEDs. In TCM theory, BPA is like a "pure yang" material for its exogenous hormonoid, which induces premature occurrence of Kidney-Essence and ICCP in children. But its pathogensis is unknown. KDNy neuron is a key signal pathway to regulate GnRH function and play an important role in puberty onset through post-transcriptional modification of histones mediated by PcG and TrxG complex. It is unknown whether BPA causing ICPP with kidney's yin-yang imbalance is by regulating KDNy neuron function through the post-transcriptional modification mediated by PcG and TrxG complex. Previous studies have shown that Ziyin Xiehuo TCM prescription is effective in treating precocious puberty. Our study is to observe the role of histones' post-transcriptional modification mediated by PcG and TrxG complex on KDNy neuron in ICPP with kidney's yin-yang imbalance，and explore whether the effect of Ziyin Xiehuo TCM prescription on PcG and TrxG complex epigenetic regulation of KDNy neuron is one of mechanism of Ziyin Xiehuo TCM prescription treating ICPP.