FOXO4-DRI对小鼠化疗诱导卵巢损伤的保护作用及机制研究

最新癌症流行病统计调查表明，患癌人群日趋年轻化，而化疗仍然是癌症治疗的重要手段，其中化疗最显著和最常见的副作用包括生育能力下降和卵巢早衰。开发化疗期间保护卵巢功能的药物，成为生育力保存的关注热点之一。化疗药物可通过DNA损伤，达到抑制肿瘤的目的，但同时也在损伤机体正常细胞。化疗药物对卵巢的损伤主要包括原始卵泡的丢失，原始卵泡的过度激活，生长卵泡的闭锁，卵巢基质细胞损伤，炎症反应及卵巢内皮血管损伤几个方面。FOXO4-DRI多肽可以通过抑制FOXO4与P53的结合，从而抑制细胞衰老，这一现象在多种器官中被验证，但是在卵巢中没有相关研究。本项目以小鼠卵巢为研究对象，用阿霉素模拟化疗过程的卵巢损伤，以DNA双链损伤为切入点，研究FOXO4-DRI肽拮抗剂对于新生小鼠卵巢及年轻小鼠卵巢的保护作用及其作用机制，为FOXO4-DRI在临床化疗过程中作为一种卵巢保护剂提供理论依据。

According to the latest cancer epidemiological reports, the cancer population is becoming younger and younger, and chemotherapy is still an important method . The most significant adverse effects of chemotherapy include the decline of fertility and premature ovarian failure. The development of drugs to protect ovarian function during chemotherapy would be a significant advantage of fertility conservation. As usual, Chemotherapy drugs through DNA damage to inhibit tumor, but also damage healthy cells. The ovarian damage of chemotherapy mainly includes loss of primordial follicle, activation of primordial follicle, atresia of growing follicle, inflammatory response, injury of ovarian stromal cells and endothelial vessels. Foxo4-DRI polypeptide can inhibit cell aging though inhibiting the combination of foxo4 and p53. This phenomenon has been verified in many organs, but there is no research in ovary. In this project, the mouse ovary was taken as the research object, Adriamycin was used to simulate the ovarian damage , and DNA double-strand break was used as the point to study the protective effect and mechanism of foxo4-DRI peptide antagonist on the ovary of newborn mice and young mice, so as to provide theoretical basis for foxo4-DRI as an ovarian protector in the clinical chemotherapy.