摘要
目的分析多囊卵巢综合征(PCOS)患者卵巢颗粒细胞氧化应激与胰岛素抵抗的相关性及其在疾病发生、发展中的作用机制。方法选取2022年6月—2023年11月在吉林省人民医院生殖医学中心接受体外受精-胚胎移植(IVF-ET)治疗的33例胰岛素抵抗型PCOS患者为PCOS组,因男方因素或单纯输卵管因素行IVF-ET的27例非PCOS女性为对照组。采集两组研究对象的空腹静脉血,检测空腹血糖(FPG)、餐后2 h血糖(2 h PG)、空腹胰岛素(FINS)、丙二醛(MDA)、超氧化物歧化酶(SOD)及总抗氧化活性(TAA)等生化指标。通过取卵手术获取卵泡冲洗液,分离培养颗粒细胞后,采用酶联免疫吸附试验(ELISA)定量检测细胞匀浆中活性氧(ROS)与总抗氧化能力(TAC)水平,计算ROS/TAC比值。采用葡萄糖氧化酶法检测颗粒细胞24 h葡萄糖摄取量。应用RT-qPCR技术检测胰岛素受体底物1(IRS1)与葡萄糖转运蛋白4(GLUT4)mRNA的相对表达量。结果对照组血清FPG为(5.11±0.56)mmol/L,2 h PG为(4.84±0.65)mmol/L,FINS为(4.43±1.02)μU/ml;PCOS组血清FPG为(5.49±0.61)mmol/L,2 h PG为(8.07±1.43)mmol/L,FINS为(10.03±2.12)μU/ml,均显著高于对照组,差异均有统计学意义(均P<0.05)。对照组血清MDA水平为(7.66±2.96)nmol/ml,SOD水平为(41.25±9.83)U/ml,TAA水平为(0.70±0.08)mmol/L;PCOS组血清MDA水平为(10.21±3.54)nmol/ml,SOD水平为(35.48±9.04)U/ml,TAA水平为(0.62±0.06)mmol/L。与对照组比较,PCOS组血清MDA水平显著升高,SOD与TAA水平均显著下降,差异均有统计学意义(均P<0.05)。Pearson相关性分析显示:胰岛素抵抗指数(HOMA-IR)与血清MDA水平呈正相关(r=0.247,P<0.05),与SOD、TAA水平均呈负相关(r=-0.191,P<0.05;r=-0.184,P<0.05)。对照组颗粒细胞匀浆中ROS/TAC比值为(1.02±0.38),PCOS组颗粒细胞匀浆中ROS/TAC比值为(0.75±0.29),显著低于对照组,差异有统计学意义(P<0.05)。对照组颗粒细胞24 h葡萄糖摄取量为(4.58±0.49)mmol/L,PCOS组颗粒细胞24 h葡萄糖摄取量为(2.96±0.37)mmol/L,显著低于对照组,差异有统计学意义(P<0.05)。对照组颗粒细胞IRS1 mRNA、GLUT4 mRNA相对表达量分别为(1.28±0.31)、(1.05±0.34),PCOS组颗粒细胞IRS1 mRNA、GLUT4 mRNA相对表达量分别为(0.47±0.13)、(0.32±0.15),均显著低于对照组,差异均有统计学意义(均P<0.05)。结论PCOS患者存在糖代谢紊乱与氧化应激失衡,且两者密切相关。颗粒细胞抗氧化能力下降与胰岛素信号通路基因(IRS1/GLUT4)表达异常,可能通过影响葡萄糖代谢参与PCOS发病。
Objective To analyze the correlation between oxidative stress of ovarian granulosa cells and insulin resistance in patients with polycystic ovary syndrome(PCOS)and the mechanism in occurrence and development of the disease.Methods Thirty-three patients with insulin-resistant PCOS who received in vitro fertilization-embryo transfer(IVF-ET)treatment in Reproductive Medicine Center of Jilin Provincial People's Hospital from June 2022 to November 2023 were selected as PCOS group,and 27 non-PCOS women who underwent IVF-ET due to male factors or simple fallopian tube factors were selected as control group.Fasting venous blood specimens were collected from research subjects in the two groups to detect biochemical indicators such as fasting plasma glucose(FPG),2-hour postprandial blood glucose(2 h PG),fasting insulin(FINS),malondialdehyde(MDA),superoxide dismutase(SOD),and total antioxidant activity(TAA).The follicular lavage fluid was obtained through oocyte retrieval surgery.After the granulosa cells were isolated and cultured,the levels of reactive oxygen species(ROS)and total antioxidant capacity(TAC)in cell homogenate were quantitatively detected by enzyme-linked immunosorbent assay(ELISA),and ROS/TAC ratio was calculated.The 24-hour glucose uptake of granulosa cells was detected by glucose oxidase method.The relative expression levels of insulin receptor substrate 1(IRS1)and glucose transporter 4(GLUT4)mRNA were detected by RT-qPCR technology.Results Serum FPG in control group was(5.11±0.56)mmol/L,2 h PG was(4.84±0.65)mmol/L,and FINS was(4.43±1.02)μU/ml.Serum FPG in PCOS group was(5.49±0.61)mmol/L,2 h PG was(8.07±1.43)mmol/L,and FINS was(10.03±2.12)μU/ml,which were significantly higher than those in control group(all P<0.05).Serum MDA level in control group was(7.66±2.96)nmol/ml,SOD level was(41.25±9.83)U/ml,and TAA level was(0.70±0.08)mmol/L.Serum MDA level in PCOS group was(10.21±3.54)nmol/ml,SOD level was(35.48±9.04)U/ml,and TAA level was(0.62±0.06)mmol/L.Compared with control group,serum MDA level in PCOS group significantly increased,while SOD and TAA levels significantly decreased(all P<0.05).Pearson correlation analysis showed that insulin resistance index(HOMA-IR)was positively correlated with serum MDA level(r=0.247,P<0.05)and negatively correlated with SOD and TAA levels(r=-0.191,P<0.05;r=-0.184,P<0.05).ROS/TAC ratio in granulosa cell homogenate of control group was(1.02±0.38),and that of PCOS group was(0.75±0.29),which was significantly lower than that of control group(P<0.05).24-Hour glucose uptake of granulosa cells in control group was(4.58±0.49)mmol/L,and that in PCOS group was(2.96±0.37)mmol/L,which was significantly lower than that in control group(P<0.05).The relative expression levels of IRS1 mRNA and GLUT4 mRNA in granulosa cells of control group were(1.28±0.31)and(1.05±0.34),respectively,while those in granulosa cells of PCOS group were(0.47±0.13)and(0.32±0.15),respectively,which were significantly lower those in control group(all P<0.05).Conclusion The patients with PCOS have disorders of glucose metabolism and imbalance of oxidative stress,and the two are closely related.Decreased antioxidant capacity of granulosa cells and abnormal expression of insulin signaling pathway genes(IRS1/GLUT4)may be involved in pathogenesis of PCOS by affecting glucose metabolism.
作者
马寅芙
刘磊
林秀英
付建华
李首庆
王起来
方艳秋
MA Yin-fu;LIU Lei;LIN Xiu-ying;FU Jian-hua;LI Shou-qing;WANG Qi-lai;FANG Yan-qiu(Reproductive Medicine Center of Jilin Provincial People's Hospital,Changchun,Jilin 130021,China)
出处
《中国妇幼保健》
2025年第23期4269-4272,共4页
Maternal and Child Health Care of China
基金
吉林省科技发展计划项目(YDZJ202301ZYTS119)。
关键词
多囊卵巢综合征
卵巢颗粒细胞
氧化应激
胰岛素抵抗
相关性
Polycystic ovary syndrome
Ovarian granulosa cell
Oxidative stress
Insulin resistance
Correlation
