基于雌激素-RANKL-自噬介导的破骨细胞前体分化作用探讨电针治疗卵巢去势小鼠骨质疏松症的机制研究

绝经后骨质疏松症(PMOP)是引起中老年妇女致残的一种严重代谢性疾病。近期研究表明基于雌激素介导的自噬可以调控破骨细胞前体（OCPs）分化，影响破骨细胞形成，调控骨吸收-骨形成代谢过程，被认为是治疗PMOP的新靶点。中医针刺调理相比西医药物治疗具有副作用少等独特优势，我们前期研究以及大量现有研究表明针刺关元具有调节雌激素水平及雌激素受体的作用，因此我们提出假设：电针关元可能通过雌激素介导的自噬相关信号通路调控OCPs自噬以及分化形成，抑制骨吸收并使骨吸收-骨形成再平衡从而达到改善PMOP的作用。本课题拟通过卵巢去势(OVx)制备PMOP模型小鼠，观察电针关元穴对OVx小鼠骨生物力学、骨密度的影响，并应用现代分子生物学技术观察电针关元对OVx小鼠雌激素水平以及OCPs分化、自噬等相关通路表达的影响，以阐明电针关元穴治疗PMOP的现代分子生物学机制，为其临床应用提供理论依据。

Postmenopausal osteoporosis (PMOP) is a severe metabolic disease that causes disability in middle-aged and elderly women. Recent studies have shown that estrogen-mediated autophagy can regulate the differentiation of osteoclast precursors (OCPs), affect the formation of osteoclasts, and regulate the metabolic process of bone resorption-bone formation. It is considered to be a new target for the treatment of PMOP. Compared with western medicine treatment, acupuncture treatment has unique advantages such as fewer side effects. Our previous research and a large number of existing studies have shown that acupuncture Guanyuan has the effect of regulating estrogen levels and estrogen receptors. Therefore, we put forward the hypothesis: electroacupuncture may regulate the autophagy and differentiation formation of OCPs through estrogen-mediated autophagy-related signaling pathways, inhibit bone resorption and rebalance bone resorption-bone formation to improve PMOP. This project intends to prepare PMOP model mice through ovarian castration (OVx), observe the effects of electroacupuncture at Guanyuan acupoint on the bone biomechanics and bone density of OVx mice, and apply modern molecular biology techniques to observe the effects of electroacupuncture at Guanyuan on the influence of mouse estrogen levels and the expression of OCPs differentiation, autophagy, and other related pathways in OVx mice. So as to clarify the modern molecular biological mechanism of electroacupuncture at Guanyuan acupoint in the treatment of PMOP and provide a theoretical basis for its clinical application.