滋阴泻火方通过DLK1介导Notch信号通路调控下丘脑kisspeptin治疗性早熟机制探讨

性早熟为儿童常见内分泌疾病之一，最新研究表明印记基因DLK1是影响青春期启动的遗传因素之一，但DLK1调控青春期确切机制尚不清楚。研究表明，kisspeptin是下丘脑-垂体-性腺（HPG）轴的“启动阀门”，Notch信号通路是下丘脑kisspeptin神经元形成的关键，而DLK1则是Notch信号通路的负反馈调节因子。故青春期启动机制可能是由于DLK表达水平改变介导Notch信号通路调控kisspeptin成熟/分泌改变，从而启动HPG轴。.本课题拟以达那唑诱导性早熟大鼠模型为基础，下丘脑弓状核注射慢病毒诱导DLK1过表达/沉默，探讨DLK1介导Notch信号通路与kisspeptin成熟/分泌的关系，以及启动HPG轴机制。对性早熟大鼠模型给予滋阴泻火方干预，探讨DLK1介导Notch信号通路水平在滋阴泻火中药合剂治疗性早熟中枢机制中的作用，同时为未来临床诊疗性早熟提供新思路可能。

Precocious puberty is one of the common endocrine diseases in children. Recent studies have shown that imprinted gene DLK1 is one of the genetic factors of puberty onset, but the exact mechanism of DLK1 regulating puberty is not clear. Studies have shown that Kisspeptin is the "starting valve" of the hypothalamic-pituitary-gonadal (HPG) axis, Notch signal pathway is the key to the formation of hypothalamic Kisspeptin neurons, and DLK1 is the negative feedback regulator of Notch signal pathway. Therefore, the initiation mechanisms of puberty may be due to the change of DLK expression level, which mediates notch signal pathway to regulate Kisspeptin maturation/ secretion and initiate HPG axis..Based on the Danazol-induced precocious puberty rat model, lentivirus was injected into the hypothalamic arcuate nucleus to induce DLK1 over-expression/ silencing, to explore the relationship between DLK1-mediated Notch signal pathway and Kisspeptin maturation/secretion, and to explore the mechanism of initiating the HPG axis. To investigate the role of DLK1-mediated Notch signal pathway level in the central mechanism of precocious puberty treated with Ziyin Xiehuo TCM prescription on the rat model of precocious puberty. At the same time, it provides new ideas for clinical diagnosis and treatment of central precocious puberty in the future.