A1AT在多囊卵巢综合征中的作用及机制研究

Polycystic Ovary Syndrome (PCOS) is a female endocrine disorders syndrome with coexisting reproductive dysfunction and metabolic disorder. As a chronic inflammatory disease, pro-inflammatory factors may induce the occurrence of the disease. Study has found that alpha 1-antitrypsin (A1AT) content is decreased and neutrophil elastase (NE) content increased in sera of patients with PCOS. Our previous studies in the serum of patients with PCOS, rat models and molecular levels indicated that A1AT might inhibit NE level to reduce inflammatory reactions of PCOS. Here, we are planning to (1) locate the A1AT in subcellular levels, (2) over-express or silence A1AT in rat ovarian cells by A1AT adenovirus-mediated to reveal the interactional relation between A1AT and NE, (3) explore the mechanism of A1AT regulates NE to inhibit inflammatory reaction during the occurrence of PCOS by using the immunoprecipitation method. This study should help us further understand the functions of A1AT, and reveal the biological mechanisms of A1AT in animal reproductive activity.

多囊卵巢综合征（PCOS）是生殖功能障碍与代谢异常并存的内分泌紊乱综合征，并发慢性炎性反应，α1-抗胰蛋白酶抑制剂（A1AT）减轻慢性炎性反应。前期研究发现PCOS患者血清中A1AT含量低于对照组，其抑制物中性粒细胞弹性蛋白酶（NE）含量高于对照组；来曲唑法构建PCOS大鼠，模型鼠A1AT含量低于对照组，NE含量高于对照组；用A1AT干预PCOS模型构建，证明A1AT干预后PCOS症状减轻；免疫组化结果显示A1AT与NE均在大鼠卵巢内表达；A1AT可能通过抑制NE减轻炎性反应影响PCOS发生。本研究进一步确定A1AT在亚细胞中的定位；通过A1AT重组腺病毒载体感染PCOS大鼠卵巢细胞，实现A1AT在细胞内的超表达和表达沉默，揭示A1AT与NE的互作关系，探索A1AT在PCOS发生中调控NE抑制炎性反应的作用机制。本研究将进一步完善A1AT的生物学功能，并揭示它在动物生殖活动中的生物机制。