归肾丸加味调控AMPK/Akt/Nrf2通路改善多囊卵巢综合征大鼠糖脂代谢及氧化应激的机制  

Mechanism of Modified Guishenwan in Regulating AMPK/Akt/Nrf2 Pathway to Improve Glucose and Lipid Metabolism and Oxidative Stress in Polycystic Ovary Syndrome Rats

作　　者：田珈瑜 秦文熠[1] 杨涓[1] 荣晓凤[1] TIAN Jiayu;QIN Wenyi;YANG Juan;RONG Xiaofeng(The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学附属第一医院,重庆400016

出　　处：《中国实验方剂学杂志》2025年第8期1-8,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上项目(81973653)。

摘　　要：目的:基于腺苷酸活化蛋白激酶/蛋白激酶B/核因子E_(2)相关因子2(AMPK/Akt/Nrf2)通路,探寻归肾丸加味改善多囊卵巢综合征(PCOS)大鼠糖脂代谢及氧化应激的作用机制。方法:采用连续灌胃来曲唑(1 mg·kg^(-1)·d^(-1))21 d建立PCOS大鼠模型。造模成功大鼠随机分成模型组,二甲双胍组(0.25 g·kg^(-1)),归肾丸加味低、中、高剂量组(4.01、8.02、16.04 g·kg^(-1)·d^(-1)),每组8只,另设正常组10只。药物组予以相应剂量药物,正常组及模型组予以等体积生理盐水,连续干预4周。采用酶联免疫吸附测定法(ELISA)检测睾酮(T)、雌二醇(E_(2))、卵泡刺激素(FSH)、黄体生成素(LH)含量,计算LH/FSH;全自动生化检测仪测定空腹血糖(FPG)、空腹胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)水平,计算胰岛素抵抗指数(HOMA-IR)、胰岛素敏感性指数(HOMA-ISI);进行口服葡萄糖耐量实验(OGTT)及胰岛素耐量实验(ITT);化学荧光法检测血清及卵巢组织中丙二醛(MDA)、晚期糖基化终产物(AGEs)、超氧化物歧化酶(SOD)水平;苏木素-伊红(HE)染色观察卵巢组织病理损伤;实时荧光定量聚合酶链式反应(Real-time PCR)、蛋白免疫印迹法(Western blot)检测卵巢组织AMPK/Akt/Nrf2通路相关mRNA及蛋白的表达。结果:与正常组比较,模型组T、LH、LH/FSH、FPG、FINS、TG、TC、HOMA-IR均明显升高,FSH、E_(2)、HOMA-ISI明显降低(P<0.05,P<0.01);其血清及卵巢组织中MDA、AGEs均明显升高,SOD明显降低(P<0.05),卵巢组织中AMPK、Akt、Nrf2在mRNA及蛋白表达均明显降低(P<0.05);OGTT、ITT结果显示,大鼠血糖在各时间节点均明显升高(P<0.05,P<0.01),糖耐量和胰岛素耐量明显受损;卵巢卵泡呈多囊样改变,黄体减少,卵泡颗粒细胞层排列稀疏;与模型组比较,二甲双胍组、归肾丸加味高剂量组T、LH、LH/FSH、FPG、FINS、TG、TC、HOMA-IR均明显降低,FSH、E_(2)、HOMA-ISI明显升高(P<0.05,P<0.01);归肾丸加味高剂量组在血清�Objective:Based on the adenosine 5'-monophosphate(AMP)-activated protein kinase/protein kinase B/nuclear factor erythroid 2-related factor 2(AMPK/Akt/Nrf2)pathway,this study aims to explore the mechanism by which modified Guishenwan improves glucose and lipid metabolism and oxidative stress in polycystic ovary syndrome(PCOS)rats.Methods:A PCOS rat model was established by continuous oral administration of letrozole(1 mg·kg^(-1)·d^(-1))for 21 days.Successfully modeled rats were randomly divided into a model group,a metformin group(0.25 g·kg^(-1)),and low-,medium-,and high-dose modified Guishenwan groups(4.01,8.02,and 16.04 g·kg^(-1)·d^(-1)),with 8 rats in each group.Ten normal rats were assigned to the normal group.The drug groups were given their respective doses,while the normal and model groups were given an equal volume of normal saline.Intervention lasted for 4 weeks.Testosterone(T),estradiol(E_(2)),follicle-stimulating hormone(FSH),and luteinizing hormone(LH)were measured by enzyme-linked immunosorbent assay(ELISA),and the LH/FSH ratio was calculated.Fasting blood glucose(FPG),fasting insulin(FINS),triglyceride(TG),and total cholesterol(TC)levels were measured using an automatic biochemical analyzer,and the insulin resistance index(HOMA-IR)and insulin sensitivity index(HOMA-ISI)were calculated.Oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were conducted.Malondialdehyde(MDA),advanced glycation end products(AGEs),and superoxide dismutase(SOD)levels in serum and ovarian tissue were measured using a chemical fluorescence method.Hematoxylin-eosin(HE)staining was used to assess ovarian tissue pathology.Real-time quantitative fluorescent polymerase chain reaction(Real-time PCR)and Western blot were used to measure the expression of AMPK/Akt/Nrf2 pathway-related genes and proteins in ovarian tissue.Results:Compared with the normal group,the model group exhibited significantly increased levels of T,LH,LH/FSH,FPG,FINS,TG,TC,and HOMA IR,while FSH,E_(2),and HOMA-ISI were significantly decreased(P<

关 键 词：多囊卵巢综合征 归肾丸加味 氧化应激 腺苷酸活化蛋白激酶(AMPK) 蛋白激酶B(Akt) 核因子E2相关因子2(Nrf2) 

分 类 号：R271[医药卫生—中医妇科学] R285[医药卫生—中医学] R589