项目来源
国家重点研发计划(NKRD)
项目主持人
冷金花
项目受资助机构
中国医学科学院
项目编号
2017YFC1001201
立项年度
2017
立项时间
未公开
研究期限
未知 / 未知
项目级别
国家级
受资助金额
588.00万元
学科
生殖健康及重大出生缺陷防控研究
学科代码
未公开
基金类别
未公开
关键词
子宫内膜异位症 ; 发病机制 ; 干预策略 ; endometriosis ; pathogenesis ; intervention strategy
参与者
刘雅萍；周应芳；史精华；李晓燕；黄艳；张晶
参与机构
北京协和医院；北京大学第一医院；中国医学科学院基础医学研究所
项目标书摘要：子宫内膜异位症(EM)是育龄期女性的常见病多发病，病变范围广泛，临床表现多样。其发病机制尤其是不同类型EM的发病机制仍不明确，制约着临床干预策略。本研究构建了EM病历资料和生物样本库，总结不同类型EM诊治特点及预后因素，提出EM预防和长期管理以及不孕的治疗对策，为指南提供数据支持。EM全基因组DNA及RNA甲基化测序发现新的富集通路并选出新的目的基因，为解释EM发病机制提供新的可能机制。构建circRNA差异表达谱筛选并验证了可能促进子宫内膜间质细胞黏附与增殖的治疗新靶点，具有试剂盒产业化经济价值。单细胞测序发现EM细胞分化周期性特征及免疫调节异常；血管周细胞在OEM异常表达与粘连和纤维化相关，可能是巧囊形成新的作用环节之一；深部浸润型子宫内膜异位症和卵巢型子宫内膜异位症表现出不同的分子表达特征，具有分子分型意义。课题通过对不同类型，不同临床表型EM微生物特征计算识别发现EM疼痛患者加德纳菌比例升高，不孕患者乳酸杆菌比例降低，为内异症临床治疗、新干预手段提供了理论依据。免疫微环境研究中发现非典型CD14+CD16+单核细胞和外泌体的差异表达，具有潜在的早期诊断标志物等经济价值。通过上述探索，在验证“在位子宫内膜决定论”和“经血逆流学说”的同时探讨了新的可能的发病机制，发现了新的诊治靶点，提出了新的诊治理念，具有规范和提升子宫内膜异位症的诊治工作，提高患者及家庭的生活质量，促进优生优育和减轻社会经济负担的重要意义。
Application Abstract: Endometriosis(EM)affects women of reproductive age with a wide range of lesions and various clinical manifestations.The pathogenesis of EM is still unclear restricting the clinical intervention strategies.In this study,we constructed the medical records database and biobank of different EM to summarize their diagnosis and treatment characteristics and prognostic factors.We also proposed the prevention and long-term management as well as treatment strategies for those combined with infertility,which were quoted in guidelines.Genome-wide DNA and RNA methylation sequencing of EM revealed new enrichment pathways and selected new target genes,providing new possible pathogenesis.Research on circRNA found a new therapeutic target that may promote the adhesion and proliferation of endometrial stromal cells,which could have economic value of kit industrialization.Single-cell sequencing revealed the periodic characteristics of EM cell differentiation and abnormal immuneregulation.We also found adhesion and fibrosis of pelvic associated with pericytes,which might be a new pathogenesis in ovarian EM.Deep infiltrating and ovarian EM showed different molecular expression characteristics,which had molecular typing significance.Microbiology analysis showed that the proportion of Gardnerella in EM patients with clinical manifestations of pain increased,while the proportion of Lactobacillus in infertile patients decreased,providing a theoretical basis for clinical treatment and new intervention methods of endometriosis.In the immune microenvironment studies,differential expression of atypical CD14+CD16+monocytes and exosomes has been found,which has potential economic value as early diagnostic markers.Through the exploration,we verified the classical theories,explored new possible pathogenesis of EM,found new targets for diagnosis and treatment,and proposed a new concept of diagnosis and treatment,which is of great significance in standardizing and improving the diagnosis and treatment of EM,improving the quality of life of patients and their families,promoting healthy birth and healthy rearing,and alleviating social and economic burden.
项目受资助省
北京市
