基于Lin28/let-7通路探讨滋阴泻火中药对特发性性早熟的治疗机理

性早熟是儿童常见的内分泌疾病之一，目前致病机理尚不清楚。let-7是一个miRNA家族，Lin28是一个miRNA结合蛋白，两者间形成了双重负反馈通路。研究显示，Lin28/let-7通路与下丘脑-垂体-性腺(HPG)轴启动、以及与促进HPG轴启动的Kisspeptin/GPR54通路相关。滋阴泻火中药可延缓提前发育的性征及骨骺成熟。本课题以达那唑诱导的雌性性早熟模型大鼠为研究对象，给予模型let-7a/b miRNA表达抑制及过表达，同时进行滋阴泻火中药干预。在不同时间点(20/25/30/35/40日龄)采样后，利用Real-time PCR、免疫组化及Western-Blot法检测Lin28/Lin28b、GnRH、Kisspeptin及GPR54的表达，从Lin28/let-7通路探讨滋阴泻火中药对Kisspeptin/GPR54通路的影响，深入研究中药延缓HPG轴启动的机制。

Precocious puberty is one of the common endocrine diseases in children, and the pathogenic mechanism is not clear at present. Let-7 is a miRNA family, and Lin28 is a miRNA binding protein. A dual negative feedback path is formed between them. Research shows that Lin28/let-7 pathway is related with Hypothalamic - pituitary - gonadal (HPG) axis starting and Kisspeptin/GPR54 pathway that promote the HPG axis starting. Nourishing "Yin"-removing "Fire" Chinese herbal mixture can delay the development of sexual characteristics in advance and Epiphyseal maturation. This topic use female sexual precocious puberty rat models induced by danazol for the study, and the models are given inhibition and overexpression of let-7a/b miRNA. After sampled at different time points(20/25/30/35/40 days old), detect the expression of Lin28/Lin28b、GnRH、Kisspeptin and GPR54 by the methods of Real-time PCR, Immunohistochemistry and Western-Blot. To explore influence of nourishing "Yin"-removing "Fire" Chinese herbal mixture for Kisspeptin/GPR54 pathway based on Lin28/let-7 pathway, to further study the mechanism of delaying the HPG axis by traditional Chinese medicine.