过度氧化损伤是造成卵巢过早衰老的主要机制。核因子E2 相关因子Nrf2是细胞自身抗氧化的关键因子，通过其下游的抗氧化反应元件（ARE）发挥抗氧化作用。课题组前期工作发现，Nrf2及ARE在卵巢组织中的表达呈现增龄降低；而姜黄素则可缓解卵巢功能的增龄性下降和氧化损伤。由此我们推测Nrf2及其下游因子的表达或功能异常是造成卵巢老化的重要原因，而姜黄素作为Nrf2通路的激活剂则可拮抗卵巢氧化和衰老进程。为了验证上述假说，我们以不同生理时段小鼠为模型，分析卵巢Nrf2及ARE相关因子的表达定位与定量，及增龄性变化趋势；然后，从影响卵巢衰老的可能靶点入手，通过Nrf2 knockdwon 及功能抑制，分析Nrf2和姜黄素对始基卵泡激活和卵泡生长发育的影响及可能机制。本项目的实施将有助于更全面认识Nrf2通路和姜黄素在卵巢衰老中的作用，并为探索延缓卵巢衰老、改善卵泡/卵子质量的措施提供依据。

One of the most important mechanism of ovarian insufficiency is considered to be due to gradual accumulation of oxygen radicals inside the ovarian micro-environment and thus reduces the reproductive abilities of ovarian including the production of ovum/follicle growth, oocyte mature, follicular atresia, ovulation and the quality of oocytes/embryo.Nuclear factor E2 related factor (Nrf2), is a transcriptor factor known to strongly combat oxidative stress in the cell through its downstream antioxidant response element (ARE). Our previous research projects have demonstration that excessive oxidative stress is the fundational cause of ovirian insufficiency and aging, which can be markedly reversed by antioxidative agent curcumin, an extractive of herb curcuma. Thus we speculate that the declining of antioxidant capacity of Nrf2/ARE is the main causes of excessive oxidative stress and leads to ovarian function disorders. Stimulating Nrf2/ARE pathway by curcumin may be a efficient treatment option for ovarian insufficiency. Followed by the previous research, in this study, we will further build the ovarian ageing mouse model (ovarian tissue and follicles growth model in vitro) to explore the relationship between Nrf2 /ARE singling pathway and ovarian aging, and the effect of curcumin in ovary function saving. We will also investigate the mechanism of curcumin treatment in ovarian ageing by Nrf2 knockdwon and function inhibition, in aiming to develop new target for women ovarian function protection.

卵巢作为女性的性腺器官，有着生殖和内分泌的双重功能，随着年龄的增长，卵巢功能逐渐衰退。卵巢细胞的抗氧化能力下降，氧化与抗氧化的失衡使卵巢细胞逐渐凋亡是造成卵巢功能衰退，走向衰老的重要原因之一。核因子E2相关因子2（Nrf2）是细胞自身抗氧化的关键因子，通过其下游的抗氧化反应原件（ARE）发挥抗氧化作用。姜黄素具有抗氧化功能。本项目以ICR小鼠为模型，通过免疫组织化学技术、蛋白免疫印迹技术及PCR技术等技术，明确了Nrf2蛋白在卵巢中的定位、Nrf2蛋白在不同周龄小鼠卵巢中的表达量变化、以及服用不同剂量/不同时间姜黄素对小鼠卵巢中Nrf2蛋白的表达量影响。