端粒酶在子宫内膜异位症发病机制及靶向治疗中的作用研究

Endometriosis is an estrogen-dependent disease with clinical characteristics similar to malignant tumors characterized by invasion and metastasis, the pathogenesis of which has not been fully elucidated. It is known that telomerase is closely related to gynecologic malignant tumors, but it is rarely reported whether telomerase is also associated with endometriosis. Some study found that telomerase activity in ectopic endometrium was significantly higher than that in eutopic endometrium, the elevated level was correlated with the stage of the disease. This confirms that telomerase may play an important role in the occurrence and development of endometriosis, but the mechanism is unclear. Based on our previous research, we will study the effects of telomerase activity on the occurrence and development of endometriosis, and the molecular mechanism by molecular biology techniques such as RNA sequencing, aiming at elucidating the role of telomerase in the pathogenesis of endometriosis. And the effect of telomerase inhibitor GRN163L and AMPK agonist metformin on ectopic endometrium will be evaluated both in vitro and vivo, which will lay the foundation for the clinical drug trials of endometriosis in the future and provide a new way for the targeted treatment of endometriosis.

子宫内膜异位症（内异症）是一种雌激素依赖性疾病，具有类似恶性肿瘤侵袭、转移的特征，其发病机制尚未完全阐明。已知端粒酶与妇科恶性肿瘤关系密切，但其是否也与内异症有关，这方面鲜有报道。研究发现异位子宫内膜病灶中端粒酶活性较自身在位子宫内膜显著增高，且增高程度与疾病分期相关，这些结果证实端粒酶在内异症发生发展中可能发挥重要作用，但机制未明。本课题基于我们前期研究，以体外内异症原代细胞培养和端粒酶转基因缺陷小鼠模型（Terc-/-）为研究平台，采用基因芯片和质谱分析等分子生物学技术综合研究端粒酶对内异症上皮和间质细胞增殖的影响，研究影响内异症细胞生长的分子机制和相关的潜在信号转导通路。同时通过体外、体内实验评估端粒酶抑制剂GRN163L和AMPK激动剂二甲双胍对异位内膜的抑制效果，阐明端粒酶在内异症发病机制中的作用并评价上述2种药物临床应用价值，建立基于内异症的靶向治疗方案。

子宫内膜异位症（内异症）是一种雌激素依赖性疾病，具有类似恶性肿瘤侵袭、转移的特征，其发病机制尚未完全阐明。已知端粒酶与妇科恶性肿瘤关系密切，但其是否也与内异症有关，这方面鲜有报道。研究发现异位子宫内膜病灶中端粒酶活性较自身在位子宫内膜显著增高 ，且增高程度与疾病分期相关，这些结果证实端粒酶在内异症发生发展中可能发挥重要作用，但机制未明。本课题基于我们前期研究，以体外内异症原代细胞培养和小鼠模型为研究平台，采用基因芯片和质谱分析等分子生物学技术综合研究端粒酶对内异症上皮和间质细胞增殖的影响，研究影响内异症细胞生长的分子机制和相关的潜在信号转导通路。同时通过体外、体内实验评估端粒酶抑制剂BIBR1532和AMPK激动剂二甲双胍对异位内膜的抑制效果，阐明端粒酶在内异症发病机制中的作用并评价上述2种药物临床应用价值，建立基于内异症的靶向治疗方案。