Wilson病是一种常染色体隐性遗传的慢性进行性铜代谢障碍性疾病，可造成以脑和肝为主的损害。女性患者生殖系统损害亦十分显著且长期被忽视。前期临床研究显示补肾化痰祛瘀方可改善Wilson病所致月经不调。综合文献、结合前期课题研究发现和预实验研究基础，我们提出补肾化痰祛瘀方可通过激活ERK信号通路改善Wilson病卵泡发育障碍。本课题将运用经典的Wilson病TX小鼠模型，观察补肾化痰祛瘀方对Wilson病模型小鼠排卵、卵泡内分泌功能、卵母细胞发育潜能、各级卵泡发育、卵泡超微结构、卵泡细胞增殖和凋亡以及ERK1/2信号通路的影响，并运用工具药阻断ERK1/2信号通路激活的方法反向验证ER1K/2信号通路在其中的作用。研究旨在阐明补肾化痰祛瘀方对Wilson病卵泡发育障碍的作用及ER1K1/2信号通路调控机制，可为Wilson病生殖系统损害的中医药治疗提供现代分子生物学理论基础。

Wilson's disease is an autosomal recessive genetic disorder, in which copper progressively accumulates in tissues due to defects in copper metabolism. It mostly causes damage in the brain and the liver. In addition, it may also cause considerable damage in the reproductive system of women . However, such damage in the reproductive system of women has long been ignored. Our previous clinical studies showed that the traditional Chinese medicine (TCM) formulation for reinforcing kidney， resolving phlegm and removing blood stasis, could effectively manage the menoxenia symptoms in Wilson’s disease female patients. Based on our preliminary clinic studies and the researches, which are sponsored by National Natural Science Fundation of China, we propose that the TCM formulation for reinforcing kidney ， resolving phlegm and removing blood stasis may activate the ERK1/2 signaling pathways and consequently ameliorate follicular maldevelopment induced by Wilson’ disease. To test this hypothesis, we will use a classic TX mouse model for Wilson's disease to determine the effect of the TCM formulation for reinforcing kidney， resolving phlegm and removing blood stasis on ovulation, ovarian endocrine, oocytes developmental potential, development of different stage follicular, ultrastructure, follicular cell proliferation and apoptosis and define the effect of the formulation on the status of the ERK1/2 pathway. Furthermore, we will use small molecule inhibitors to block the ERK1/2 signaling pathway in order to validate that activation of the ERK signaling pathway is indeed a key molecular mechanism by which the TCM formation for reinforcing kidney， resolving phlegm and removing blood stasis improves the follicular development. The study would help to elucidate the molecular mechanism of the TCM formulation for reinforcing kidney， resolving phlegm and removing blood stasis in treating Wilson’s disease. The study is intended to provide a theory basis of modern molecular biology and a new idea in the traditional Chinese medicine therapy of the reproductive system damage in Wilson’s disease.