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在女性生殖系统中,卵巢对化疗药物最敏感,化疗在提高肿瘤和免疫性疾病治愈率的同时,引起不孕不育、卵巢功能障碍,甚至卵巢早衰。细胞凋亡被认为是化疗药物引起卵巢结构和功能破坏导致卵泡丢失和卵巢发育障碍的机制之一。沉默信息调节因子1(silent information regulator 1,SIRT1)是改善衰老的长寿因子,诸多研究均发现SIRT1可以通过调控细胞凋亡影响卵泡发育,影响生殖和内分泌功能。白芦藜醇等植物多酚可激活SIRT1,调控SIRT1在细胞凋亡中的作用。“年轻因子”生长分化因子(growth differentiation factor 11,GDF11)可以逆转心脏、骨骼肌和神经系统衰老,而在卵巢中亦有GDF11表达,推测GDF11亦可改善化疗性卵巢功能损伤。通过对SIRT1及相关激活剂的深入研究,为化疗损伤卵巢功能保护和生育能力改善的药物的开发及临床应用提供一定的理论依据。
In the female reproductive system, the ovary is the most sensitive to chemotherapeutic drugs. Chemotherapy can increase the cure rate of tumors and immune diseases and cause infertility, ovarian dysfunction and even premature ovarian failure. Apoptosis is believed to be one of the mechanisms by which chemotherapeutic drugs cause the loss of ovarian follicles and ovarian developmental disorders caused by the destruction of ovarian structure and function. SIRT1 is a long-term factor to improve aging. Many studies have found that SIRT1 can affect follicular development by regulating apoptosis, affecting reproductive and endocrine functions. Plant polyphenol such as resveratrol can activate SIRT1 and regulate the role of SIRT1 in apoptosis. GDF11 reverses heart, skeletal muscle and nervous system senescence, while GDF11 is also expressed in the ovary. It is speculated that GDF11 may also improve chemopreventional ovarian dysfunction. Through in-depth study of SIRT1 and related activators, it provides a theoretical basis for the development and clinical application of drugs for protecting the ovary from injury and improving fertility.