月见草油抵抗多囊卵巢综合征大鼠卵巢氧化应激  

Evening primrose oil resists oxidative stress in the ovaries of rats w ith polycystic ovary syndrome

作　　者：虎娜 孙苗[1,2] 邢莎莎 许丹霞 海小明 马玲[1,3] 杨丽[4] 勉昱琛 何瑞 陈冬梅 马会明[1,2] HU Na;SUN Miao;XING Shasha;XU Danxia;HAI Xiaoming;MA Ling;YANG Li;MIAN Yuchen;HE Rui;CHEN Dongmei;MA Huiming(Key Laboratory of Fertility Preservation and Maintenance(Ministry of Education),Ningxia Medical University,Yinchuan 750004,Ningxia,China;Department of Human Anatomy and Tissue Embryology,School of Basic Medical Science,Ningxia Medical University,Yinchuan 750004,Ningxia,China;Ningxia Key Laboratory of Stem Cell and Regenerative Medicine,The General Hospital of Ningxia Medical University,Yinchuan 750004,Ningxia,China;Experimental Animal Center of Ningxia Medical University,Yinchuan 750004,Ningxia,China)

机构地区：[1]宁夏医科大学生育力保持教育部重点实验室/宁夏回族自治区生殖与遗传重点实验室,宁夏银川750004 [2]宁夏医科大学基础医学院人体解剖与组织胚胎学系,宁夏银川750004 [3]宁夏医科大学总医院宁夏干细胞与再生医学重点实验室,宁夏银川750004 [4]宁夏医科大学实验动物中心,宁夏银川750004

出　　处：《山东大学学报（医学版）》2022年第5期22-30,共9页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81660813);宁夏科技领军人才项目(2020GKLRLX11);宁夏药物研发创新团队项目(NXKJT2019012);宁夏高校大学生创新创业训练计划项目(S202110752060)

摘　　要：目的探讨月见草油(EPO)对高脂饮食联合来曲唑所致多囊卵巢综合征(PCOS)模型大鼠激素水平、代谢水平、氧化水平以及卵巢组织中NAD-依赖性去乙酰化酶Sirtuin-1(SIRT1)/转录因子叉头框蛋白O1(FoxO1)信号通路表达的影响。方法72只大鼠共分为6组,12只为正常对照,其余60只大鼠喂食高脂饲料(40%脂肪)8周,并在喂食方案的最后3周,联合浓度为1 mg/(kg·d)的来曲唑灌胃21 d,制备PCOS大鼠模型。模型制备结束后经尾部血清激素水平分析,每组剔除偏差较大的模型大鼠2只,并把正常对照组和模型制备成功的大鼠分为6组,每组10只,分别为正常对照组、PCOS模型组、二甲双胍组、EPO小剂量组、EPO中剂量组、EPO大剂量组。ELISA方法和生化酶法检测各组血清空腹血糖(FPG)、空腹胰岛素(FINS)、睾酮(T)、促卵泡生成激素(FSH)、促黄体生成激素(LH)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)和丙二醛(MDA),苏木精-伊红(HE)染色观察各组卵巢形态,免疫组织化学和蛋白质免疫印迹法(Western blotting)检测卵巢组织SIRT1/FoxO1通路和相关抗氧化因子SOD1和谷胱甘肽转移酶(GST)以及衰老因子SIRT1和FoxO1的定位与相对表达水平。结果与正常对照组相比,PCOS模型组体质量、FPG、FINS、T、LH和FSH水平均升高(P<0.001);SOD和T-AOC水平下降(P<0.001),MDA水平升高(P<0.001)。ELISA结果显示,EPO和二甲双胍治疗后,体质量、FPG、FINS水平较PCOS模型组均呈下降趋势且有统计学意义(P<0.001),各组SOD水平与PCOS模型组相比升高(P<0.001),MDA水平下降(P<0.05),二甲双胍组、EPO中剂量组和大剂量组T-AOC水平较PCOS模型组升高(P<0.001);二甲双胍组和EPO中剂量组、大剂量组T和LH水平较PCOS模型组下降(P<0.001);二甲双胍组和EPO治疗大剂量组FSH水平较PCOS模型组下降(P<0.001)。免疫组化结果显示,SOD1、GST和SIRT1蛋白在颗粒细胞、间质细胞、原始卵泡和黄体均有阳性表达;WestObjective To investigate the effects of evening primrose oil(EPO)on the hormonal,metabolic and oxidation levels in rats with polycystic ovary syndrome(PCOS)induced by high-fat diet combined with letrozole,and to explore the expression of NAD-dependent deacetylase sirtuin-1(SIRT1)/Forkhead box O1(FoxO1)signaling pathway in the ovarian tissue.Methods A total of 72 rats were divided into 6 groups,with 12 as the normal control group,and the other 60 rats were fed high-fat diet(40%)for 8 weeks.In the last 3 weeks of the feeding program,letrozole at a concentration of 1 mg/kg/d was added to prepare PCOS models.After the models were established,the serum hormonal levels in the tail of rats were analyzed,and 2 rats with large deviation were removed from each group.Plus the normal control group,the PCOS models were divided into 5 groups,with 10 rats in each group:PCOS model group,metformin group,EPO low-dose group,EPO medium-dose group,and EPO high-dose group.The serum fasting plasma glucose(FPG),serum insulin(FINS),testosterone(T),luteinizing hormone(LH),follicle stimulating hormone(FSH),superoxide Dismutase(SOD),total antioxidant capacity(T-AOC)and malondialdehyde(MDA)of each group were detected with ELISA and biochemical method.The ovarian morphology was observed with hematoxylin and eosin(HE)staining.The locations and expressions of SIRT1/FoxO1 pathway,SOD1 and glutathione S-transferase(GST),SIRT1 and FoxO1 were detected with immunohistochemistry and Western blotting.Results Compared with the blank control group,the PCOS model group had significantly increased weight,FPG,FINS,T,LH,FSH(P<0.05),significantly decreased SOD and T-AOC(P<0.05),and significantly increased MDA(P<0.01).ELISA results showed that after EPO and metformin treatment,the weight,FPG,FINS and MDA decreased(P<0.05),but SOD increased(P<0.05)compared with the PCOS model group.Compared with PCOS model group,the metformin group,medium-dose and high-dose groups had significantly increased T-AOC(P<0.05),but significantly decreased T and LH(P<0.05).Compared w

关 键 词：月见草油 SIRT1/FoxO1信号通路 氧化应激 多囊卵巢综合征 大鼠 

分 类 号：R285.5[医药卫生—中药学]