基于Keap1/Nrf2/HO-1信号通路研究当归醇提物对多囊卵巢综合征大鼠的保护作用  

The protective effects of ethanol extract of Angelicae Sinensis Radix on rats with polycystic ovary syndrome based on Keap1/Nrf2/HO-1 signaling pathway

作　　者：莫思懿 曹后康 张可锋[1] 晋玲 钟明利[1] 韦日明[1] 高雅[1] MO Si-yi;CAO Hou-kang;ZHANG Ke-feng;JIN Ling;ZHONG Ming-li;WEI Ri-ming;GAO Ya(Pharmacology Laboratory of Prevention and Treatment of High Incidence of Disease,Guilin Medical University,Guilin Guangxi 541199,China;School of Pharmacy,Gansu University of Traditional Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]桂林医学院高发病防治药理学重点实验室,广西桂林541199 [2]甘肃中医药大学药学院,甘肃兰州730000

出　　处：《中国药理学通报》2024年第4期740-747,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81960779)。

摘　　要：目的使用来曲唑联合高脂饮食建立多囊卵巢综合征(polycystic ovarian syndrome,PCOS)大鼠模型,探讨当归醇提物(ethanol extract of Angelicae Sinensis Radix,EEA)对PCOS大鼠的保护作用及其作用机制。方法来曲唑联合高脂饮食诱导雌性SD大鼠建立PCOS模型,并用EEA干预。阴道涂片染色、HE染色、酶联免疫吸附法(ELISA)和生化指标检测评价EEA对PCOS大鼠的治疗作用,并通过荧光定量PCR(qRT-PCR)和Western blot检测EEA对Keap1/Nrf2/HO-1信号通路的影响。结果阴道涂片和HE染色结果表明,EEA改善了PCOS大鼠动情周期紊乱和卵巢组织病变,ELISA和生化指标检测结果表明EEA可以调节激素紊乱,改善血脂异常;且在模型组中Keap1蛋白和mRNA表达明显上调,Nrf2和HO-1蛋白和mRNA表达明显下调而经过EEA治疗后Keap1蛋白和mRNA表达明显下调,Nrf2和HO-1蛋白和mRNA表达明显上调(P<0.05或P<0.01)。结论EEA可以减轻大鼠PCOS,其机制可能是通过促进Keap1/Nrf2/HO-1信号通路,从而抑制氧化应激。Aim To establish a polycystic ovary syndrome(PCOS)rat model by using letrozole combined with a high-fat diet,and explore the protective effects of ethanol extract of Angelicae Sinensis Radix(EEA)on PCOS rats and its mechanism of action.Methods Letrozole combined with high-fat diet was used to induce PCOS model in female SD rats,and EEA was used for intervention.Vaginal smear staining,HE staining,enzyme-linked immunosorbent assay(ELISA)and biochemical indexes were used to evaluate the therapeutic effect of EEA on PCOS rats.Quantitative real-time PCR(qRT-PCR)and Western blot were used to detect the effect of EEA on Keap1/Nrf2/HO-1 signaling pathway.Results The results of vaginal smear and HE staining showed that EEA improved the estrous cycle disorder and ovarian tissue lesions in PCOS rats.The results of ELISA and biochemical indicators showed that EEA could regulate hormone disorder and improve dyslipidemia.In addition,Keap1 protein and mRNA expression was significantly up-regulated,Nrf2 and HO-1 protein and mRNA expression was significantly down-regulated in the model group.After EEA treatment,Keap1 protein and mRNA expression was significantly down-regulated,Nrf2 and HO-1 protein and mRNA expression was significantly up-regulated(P<0.05 or P<0.01).Conclusion EEA can alleviate PCOS in rats,and its mechanism may be through promoting Keap1/Nrf2/HO-1 signaling pathway,thereby inhibiting oxidative stress.

关 键 词：当归醇提物 多囊卵巢综合征(PCOS) Keap1/Nrf2/HO-1信号通路 氧化应激 性激素 血脂 

分 类 号：R-332[医药卫生] R284.1R349.1R711.75R977.12