基于SIRT1介导的细胞自噬探讨补肾温阳化瘀法治疗子宫内膜异位症的作用机制

EMs是妇科常见疑难病，对本病发病机制及治疗手段的探究己成为热点问题。现已明确细胞自噬是EMs发病的重要环节，细胞自噬水平受多条信号通路调控，SIRT1作为自噬的关键调节因子，可通过去乙酰化FoxO1、作用于miR-221/222调控自噬，miR-221/222在受到FoxO1调控的同时还可反馈调节SIRT1的活性，从而形成SIRT1-FoxO1-miR-221/222反馈环路参与自噬的生物学过程。预实验已证实SIRT1的下游靶基因FoxO1参与EMs自噬的发生，为进一步研究SIRT1介导的自噬机制奠定了基础。细胞自噬功能的异常是机体阴阳失衡的微观表现，本项目以中医“阴阳消长平衡理论”为基础，以SIRT1介导的细胞自噬为切入点，拟阐明补肾温阳化瘀法通过调节细胞自噬治疗EMs的作用机制，这对于从微观层面挖掘补肾温阳化瘀法补益肾阳、消散瘀滞，恢复机体阴阳消长平衡的分子生物学内涵具有重要意义。

EMs is a common difficult disease in gynecology, the pathogenesis and treatment of which has become a hot issue. It is now clear that autophagy is an important link in the pathogenesis of EMs. The level of autophagy is regulated by multiple signaling pathways. SIRT1, as a key factor of autophagy, can regulate autophagy by deacetylating of FoxO1 and acting on mir-221/222. Mir-221/222, while being regulated by FoxO1, can also feedback regulate the activity of SIRT1, thereby SIRT1-FoxO1-mir-221/222 feedback loop forms and participates in the biological process of autophagy. Preliminary experiments have confirmed that FoxO1, the target gene of SIRT1, is involved in the occurrence of autophagy in EMs, which lays a foundation for us to further study the regulatory mechanism of autophagy mediated by SIRT1. Abnormal autophagy function is the microscopic manifestation of imbalance between Yin and Yang in the body, based on Yin and Yang equilibrium theory of Traditional Chinese Medicine, we choose SIRT1 mediated autophagy as a breakthrough point to clarify the EMs biological essence of kidney Yang deficiency and blood stasis syndrome, and illustrate the mechanism of regulating autophagy by tonifying kidney warming Yang and removing blood stasis method. It is of great significance to explore the molecular biological connotation of tonify kidney warm Yang and remove blood stasis method.