活血化瘀法是中医治疗子宫内膜异位症（EM）的重要治则。申请人前期研究发现活血化瘀法显著降低了EM大鼠子宫内膜细胞中血管内皮生长因子（VEGF）mRNA表达水平，同时显著回调了EM子宫内膜细胞中VEGF启动子区的低甲基化水平。VEGF是改善线粒体功能的重要靶点，而线粒体与卵泡发育、受精和胚胎发育密切相关。以此为基础，提出假说：活血化瘀法通过调控VEGF甲基化及表达，影响线粒体氧化应激等功能，最终引发子宫内膜细胞、卵母细胞、胚胎及子代的相应改变。本项目拟“纵向深层次”应用焦磷酸测序、透射电镜、染色质免疫共沉淀等技术研究活血化瘀法调控VEGF介导的下游线粒体氧化应激、转录调控等机制，“横向多维度”定位子宫内膜、配子胚胎及出生子代等节点追踪活血化瘀法对EM模型生殖及子代近远期健康的影响及机制。研究成果对揭示中医“有故无殒，亦无殒也”理论的生物学基础具有一定的科学价值。

The therapeutic principle of Huo-Xue-Hua-Yu is important for the treatment of endometriosis (EM) by traditional Chinese medicine. The applicant's previous study found Huo-Xue-Hua-Yu therapy significantly reduced the expression of vascular endothelial growth factor (VEGF) mRNA in the endometrial tissue of EM rats, and significantly regulated the low methylation level of VEGF promoter region in EM endometrial cells. VEGF is an important target for improving mitochondrial functions, and mitochondria are closely related to follicular development, fertilization and embryonic development. Based above, the hypothesis is proposed: Huo-Xue-Hua-Yu therapy affects the mitochondrial oxidative stress and other functions, and finally causes the corresponding changes of endometrial cells, oocytes, embryos and offspring. This present project aims to explore the underlying mechanism of VEGF-mediated transcriptional regulation of mitochondrial oxidative stress in downstream mitochondria in "situational deep-level", and to track the effects of Huo-Xue-Hua-Yu therapy on the reproductive function of endometrial, oocytes, embryos and health of offspring of EM models in "horizontal multi-dimension", with techniques such as pyrosequencing, transmission electron microscopy and chromatin immunoprecipitation. The outcomes possess certain scientific values for revealing biological basis of the theory of traditional Chinese medicine "You-Gu-Wu-Yun, Yi-Wu-Yun-Ye".