基于Nrf2/HO⁃1信号通路探讨山楂叶总黄酮对多囊卵巢综合征大鼠卵巢氧化应激的影响  

Effects of hawthorn leaves flavonoids on ovarian oxidation stress in rats with polycystic ovary syndrome based on Nrf2/HO-1 signaling pathway

作　　者：刘桂宇[1] 谢倩倩 陈希芬[1] 元丽 康雪敏[1] LIU Gui-yu;XIE Qian-qian;CHEN Xi-fen;YUAN Li;KANG Xue-min(Community Hospital,Hebei Normal University,Shijiazhuang 050024,China;College of Life Sciences,Hebei Normal University,Shijiazhuang 050024,China)

机构地区：[1]河北师范大学职工医院,河北石家庄050024 [2]河北师范大学生命科学学院,河北石家庄050024

出　　处：《中成药》2023年第9期2883-2889,共7页Chinese Traditional Patent Medicine

基　　金：河北省创新能力提升计划项目(20557681D);河北省自然科学基金项目(C2011205111)。

摘　　要：目的探讨山楂叶总黄酮对多囊卵巢综合征(PCOS)大鼠卵巢氧化应激的影响及其作用机制。方法大鼠随机分为空白组、模型组、二甲双胍组(100 mg/kg)及山楂叶总黄酮低、中、高剂量组(100、200、400 mg/kg),每组10只。采用高脂饲料喂食联合灌胃来曲唑法建立PCOS大鼠模型,灌胃给药21 d后测定大鼠子宫、卵巢质量,FINS、FBG水平并计算HOMA-IR值,通过全自动生化仪检测血清TC、TG、HDL、LDL水平,ELISA法检测血清T、AMH、E_(2)水平和FSH、LH活性,HE染色观察卵巢组织病理形态变化,采用试剂盒检测卵巢组织SOD、GSH-Px活性和MDA水平,Western blot法检测卵巢组织Nrf2、HO-1蛋白表达。结果与模型组比较,山楂叶总黄酮各剂量组大鼠子宫质量,血清FSH活性和E_(2)水平,卵巢组织SOD、GSH-Px活性和Nrf2、HO-1蛋白表达均升高(P<0.05,P<0.01);卵巢质量,FBG、FINS水平和HOMA-IR值,血清LH活性和T、AMH、LDL、TC、TG水平,卵巢组织MDA水平均降低(P<0.05,P<0.01);大鼠动情周期紊乱及卵巢组织病理损伤得到改善。结论山楂叶总黄酮能恢复PCOS大鼠紊乱的动情周期,减轻卵巢组织病理损伤,调节激素水平,改善糖脂代谢异常及胰岛素敏感性,其机制可能与激活Nrf2/HO-1信号通路介导的抗氧化应激作用有关。AIM To investigate the effects of hawthorn leaves flavonoids on ovarian oxidative stress in rats with polycystic ovary syndrome(PCOS)and the mechanism.METHODS The rats were randomly divided into the blank group,the model group,the metformin group(100 mg/kg)and the low dose,medium dose and high dose hawthorn leaves flavonoids groups(100,200 and 400 mg/kg),with 10 rats in each group.The rat model of PCOS was established by feeding of high-fat diet and oral letrozole.After 21 days of corresponding oral administration,the rats had their weight of uterus and ovary,the levels of FINS and FBG measured and the HOMA-IR value calculated;their serum levels of TC,TG,HDL and LDL detected by automatic biochemical analyzer;their levels of serum T,AMH and E_(2)and the activities of FSH and LH detected by ELISA;their pathological changes of ovarian tissue observed by HE staining;their ovarian SOD and GSH-Px activities and MDA level detected by kit;and their ovarian protein expressions of Nrf2 and HO-1 detected by Western blot.RESULTS Compared with the model group,all of the groups intervened with hawthorn leaves flavonoids displayed improvements in the uterus quality,serum FSH activity and E_(2)level,the activities of SOD,GSH-Px and the protein expressions of Nrf2 and HO-1 in ovarian tissue(P<0.05,P<0.01);decreases in ovarian mass,FBG and FINS levels and HOMA-IR values,serum LH activity and levels of T,AMH,LDL,TC and TG,and ovarian MDA levels(P<0.05,P<0.01);and improvement in estrous cycle disorder and pathological damage of ovarian tissue as well.CONCLUSION Hawthorn leaves flavonoids can restore the disordered estrous cycle of PCOS rats,reduce the pathological damage of ovarian tissue by regulating hormone levels,improving abnormal glucose and lipid metabolism and insulin sensitivity via activation of Nrf2/HO-1 signaling pathway mediated antioxidant stress.

关 键 词：山楂叶总黄酮 多囊卵巢综合征 氧化应激 Nrf2/HO-1信号通路 糖脂代谢 

分 类 号：R285.5[医药卫生—中药学]