Wang Kexin, Wang Lin, Wu Chengyong, Chen Hongxiang, Cai Donghui, Lu Linglan, Liu Xuli, Jiao Zhen
Department of Gynecology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
J Biochem Mol Toxicol. 2025 Feb;39(2):e70158. doi: 10.1002/jbt.70158.
Lycopene (LYC) is an extremely powerful antioxidant with the potential to treat a range of diseases and to inhibit ferroptosis. This research aims to elucidate how LYC impacts polycystic ovarian syndrome (PCOS) and the action mechanisms. A PCOS rat model was constructed by injecting DHEA. Different doses of LYC were injected intraperitoneally in PCOS rats, the estrous cycle was recorded. The histopathological damage of ovary in PCOS rats was observed by HE staining, testosterone (T), estradiol (E2), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were examined by ELISA kits. Transmission electron microscopy, prussian blue staining, biochemical kits to determine ferroptosis. Immunohistochemistry and Western blot to assess the levels of ferroptosis-related and AMPK/Nrf2 pathway-related proteins to explore whether LYC affects ferroptosis in PCOS through this pathway. PCOS rats had significantly higher body weights, ovarian weights and ovarian indices, and disorganized estrous cycles, which were dose-dependently ameliorated by LYC. In addition, LYC significantly ameliorated the histopathological damage of ovary in PCOS rats and restored the normal secretion of T, E2, LH, and FSH. LYC attenuates iron deposition in PCOS ovarian tissues, reduces iron and ROS levels, and inhibits ferroptosis. Notably, LYC activated the AMPK/Nrf2 pathway, and AMPK inhibitor intervention attenuated the therapeutic effect of LYC in PCOS rats, suggesting that LYC acts through the AMPK/Nrf2 pathway. LYC attenuates estrous cycle disruption, ameliorates pathological impairments, and inhibits ferroptosis in PCOS rats by modulating the AMPK/Nrf2 pathway.
番茄红素（LYC）是一种极其强大的抗氧化剂，具有治疗一系列疾病和抑制铁死亡的潜力。本研究旨在阐明LYC如何影响多囊卵巢综合征（PCOS）及其作用机制。通过注射脱氢表雄酮（DHEA）构建PCOS大鼠模型。对PCOS大鼠腹腔注射不同剂量的LYC，记录动情周期。通过苏木精-伊红（HE）染色观察PCOS大鼠卵巢的组织病理学损伤，采用酶联免疫吸附测定（ELISA）试剂盒检测睾酮（T）、雌二醇（E2）、黄体生成素（LH）和卵泡刺激素（FSH）水平。采用透射电子显微镜、普鲁士蓝染色、生化试剂盒检测铁死亡情况。采用免疫组织化学和蛋白质免疫印迹法评估铁死亡相关蛋白和AMPK/Nrf2信号通路相关蛋白的水平，以探讨LYC是否通过该信号通路影响PCOS中的铁死亡。PCOS大鼠体重、卵巢重量和卵巢指数显著升高，动情周期紊乱，LYC可剂量依赖性地改善这些情况。此外，LYC显著改善了PCOS大鼠卵巢的组织病理学损伤，并恢复了T、E2、LH和FSH的正常分泌。LYC减轻了PCOS卵巢组织中的铁沉积，降低了铁和活性氧（ROS）水平，并抑制了铁死亡。值得注意的是，LYC激活了AMPK/Nrf2信号通路，AMPK抑制剂干预减弱了LYC对PCOS大鼠的治疗效果，表明LYC通过AMPK/Nrf2信号通路发挥作用。LYC通过调节AMPK/Nrf2信号通路减轻PCOS大鼠的动情周期紊乱，改善病理损伤，并抑制铁死亡。
