前扣带回通过HPO轴参与针刺改善多囊卵巢综合征情绪和生殖障碍

Polycystic Ovary Syndrome (PCOS) is the most common endocrine metabolic disorder in women of reproductive age, and require long-term individualized treatment programs. Pilot study by the applicant has shown that acupuncture improves ovulatory disorder, insulin resistance and emotional dysfunction of PCOS. But the underlying mechanisms remain unclear. Our animal experiments show that acupuncture regulates neuronal activities in the anterior cingulate cortex (ACC) in addition to relief of emotional and endocrine disorders in PCOS rats. Based on these results, we hypothesize that acupuncture improves emotional and reproductive dysfunction in PCOS through anterior cingulate cortex-mediated regulation on the HPO axis. The present project aims to examine the involvement of ACC in acupuncture treatment of rats with DHEA-induced PCOS. With opto- and chemo-genetics, neuronal activities of the ACC will be artificially controlled and the resulting endocrine and behavioral changes will be monitored. The project hopefully provides novel clues for possible mechanisms of acupuncture treatment of PCOS.

多囊卵巢综合征（PCOS）是育龄妇女最常见的内分泌，代谢，情绪紊乱的疾病，是引起继发性闭经和无排卵性不孕的主要原因。申请人前期研究发现：针刺能有效改善PCOS患者的排卵障碍，胰岛素抵抗和情绪失常，但是，针刺的作用机制尚不清晰。动物实验初步显示：电针不仅可缓解PCOS高雄大鼠的负性情绪和内分泌紊乱，还可激活前扣带回（ACC）神经元电生理活性，抑制下丘脑促性腺激素（GnRH）释放。基于这两个脑区在情绪和生殖中的重要地位，我们推测 “ACC-下丘脑神经网络是针刺改善PCOS情绪和生殖障碍的关键中枢机制”。因此，本项目拟在已建立的PCOS高雄大鼠模型上，运用神经科学领域前沿的光遗传与化学遗传技术，通过靶向激活/抑制ACC神经元活性，观察下丘脑和体内生殖与情绪相关激素/受体的变化，阐明ACC-下丘脑神经网络在电针改善PCOS高雄模型大鼠情绪和生殖障碍的作用机制，为针刺治疗PCOS提供新的科学依据。

本项目结合基础和临床研究，基础研究提示针刺能改善PCOS高雄模型大鼠的生殖障碍和负性情绪，其机制可能与调控前扣带回（anterior cingulate cortex, ACC）神经元电生理特性，抑制下丘脑促性腺激素（GnRH）频率相关，提示针刺可能通过调节ACC-下丘脑神经网络来PCOS的情绪，内分泌和代谢的紊乱。临床观察发现多囊卵巢综合征（PCOS）女性和正常对照相比，PCOS女性有更严重的焦虑和抑郁，负性情绪会加重PCOS内分泌和代谢的紊乱，通过临床RCT试验（发现和对照组相比，四个月的针刺治疗能一定程度改善针刺治疗可以改善PCOS患者的排卵障碍，降低胰岛素抵抗，高雄激素水平，缓解负性情绪，促进β-内啡肽和多巴胺（DA）的释放。本研究共发表SCI论文4篇，核心期刊1篇，1篇SCI和1篇核心期刊在投，获得专利1项，国际和国内会议交流各1次。