LncRNA-SRA介导下丘脑Kisspeptin-GPR54途径探讨低促排卵障碍发病新机制及中药心肾同调法干预的研究

随着现代女性压力增大和环境改变，低促排卵障碍成为女性生育力减退中的重要问题，但目前病机及治疗研究有限。该病是“神经-内分泌共病”，源于下丘脑对生殖轴调控紊乱，这与国医大师夏桂成中医“心肾”理论体系具有一致性。我们前期研究发现，下丘脑表达一种LncRNA-SRA，其下调可能影响下丘脑Kisspeptin-GPR54系统参与该病的病理过程。因此我们推测，下丘脑SRA是维系生殖排卵的重要组件，其水平下降可能是该病的重要病理基础。鉴于此，本项目拟通过SRA基因敲除和回复表达等手段揭示SRA维护生殖功能的作用，阐明SRA在低促排卵障碍中的病理机制，从现代医学角度证明中医 “心（脑）-肾-子宫轴”理论，并为该病“心肾不交”的可能病机提供西医理论支持。同时基于我们前期研究证实补肾促排卵汤对该病药效的初步结果，验证中药补肾促排卵汤通过调节SRA表达改善生殖轴及排卵功能，为“心肾同调”法治疗该病的有效方剂。

With the increase of pressure and the change of environment, hypogonadotropic ovulation disorder has become an important problem in female fertility decline, but the pathogenesis and treatment research is still limited. This disease is a " neuro-endocrine disease", which originates from the regulation disorder of the hypothalamus in the reproductive axis. This is consistent with the theoretical system of "heart -kidney view" of Chinese medicine by Xia guicheng, a master of traditional Chinese medicine. Our previous study found that the hypothalamus expressed an LncRNA-SRA, and its down-regulation may affect the hypothalamus Kisspeptin-GPR54 system to participate in the pathological process of this disease. Therefore, we hypothesized that hypothalamic SRA is an important component in maintaining reproductive ovulation, and its decline may be an important pathological basis for this disease. In view of this, this project proposed by SRA knockout and reply expression reveals the maintenance of reproductive function by SRA, illustrates SRA 's role in the pathological mechanism in hypogonadotropic ovulation disorder. From the perspective of modern medicine, to proof "heart (brain) - kidney - uterine axis" theory in Chinese medicine and to provide western medicine theory support for "heart-kidney disjunction", the possible pathogenesis of this disease in Chinese medicine. At the same time, based on the preliminary results of our previous studies that confirmed the effect of Bu-shen-cu-pai-luan decoction on this disease, to verify that this decoction could improve the reproductive axis and ovulation function by regulating the expression of SRA, and is an effective prescription for the treatment of the disease with "heart-kidney homology" method. This project targeted SRA as a new target for the study of the disease, and opens up new ideas for the pathogenesis and treatment of this disease.