补肾促卵冲剂保护卵巢储备功能下降卵母细胞线粒体DNA氧化损伤的作用及机制研究

目前，卵巢储备功能下降（DOR）发病率呈逐年上升趋势，发病人群日益趋向年轻化，严重影响着女性的生活质量，但其发病机制尚不明确。文献报道，氧化应激可造成细胞线粒体DNA（mtDNA）及线粒体功能受损。而DOR的发生与mtDNA氧化损伤密切相关，所以减轻氧化损伤保护mtDNA及线粒体功能可作为治疗DOR的重要新靶点。中医认为肾虚血瘀是DOR的主要病机，在前期研究中发现，补肾促卵冲剂通过调整下丘脑-垂体-卵巢轴，有明显的促排卵作用。因此，本课题采用H2O2诱导的氧化损伤模型卵母细胞和雷公藤多苷片制备的DOR模型大鼠，应用PCR、荧光电镜、JC-1染色等实验技术，证明氧化应激引起卵母细胞mtDNA及线粒体功能障碍，同时从卵巢组织-卵母细胞-线粒体层次探讨补肾促卵冲剂对DOR卵母细胞mtDNA的保护及其作用机制。本研究将为补肾活血中药治疗DOR提供科学依据，对提高生殖健康水平和人口素质具有深远影响。

At present, there is an upward trend in incidence of diminished ovarian reserve(DOR). The onset age is younger and younger, which seriously influences women's life quality. However, the pathogenesis of DOR is still unclear. According to published reports, oxidative stress causes mitochondrial DNA(mtDNA) and mitochondrial function impaired. The occurrence of DOR is closely related with oxidative damage of mtDNA. Thus a novel important target of treating DOR is to reduce the oxidative damage of mtDNA and protect mitochondrial function. In TCM, Shen(kidney) deficiency and blood stasis were always fundamental pathogenesis through the emergence and development of DOR. In previous clinical and experimental research, Bushen Culuan Recipe modulates the axial function of H-P-O and influences the maturation of follicles. Therefore, we make oxidative damaged model occytes induced by H2O2 and DOR model rats induced by TWG tablets. Applying PCR, electron microscope technology and JC-1dyeing experiments to prove that oxidative stress causes dysfunction of oocyte mtDNA and mitochondrial function. Meanwhile to explore the mechanism of Bushen Culuan Recipe protecting mtDNA from ovarian tissue-oocyte-mitochondrion levels. The study will provide scientific theory basis for reinforcing kidney and removing stasis treating DOR ,which would have far-reaching influence in improving level of reproductive health and population quality.