二甲双胍对胰岛素抵抗多囊卵巢综合征患者白细胞线粒体功能的影响。
Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance.
机构信息
Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain
Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain.
出版信息
Eur J Endocrinol. 2015 Nov;173(5):683-91. doi: 10.1530/EJE-15-0572. Epub 2015 Aug 28.
OBJECTIVE
Oxidative stress and mitochondrial dysfunction are implicated in polycystic ovary syndrome (PCOS). The present study assesses the effect of metformin treatment on mitochondrial function in polymorphonuclear cells from PCOS subjects. Additionally, we evaluate endocrine parameters and levels of interleukin 6 (IL6) and tumour necrosis factor alpha (TNFα).
DESIGN AND METHODS
Our study population was comprised of 35 women of reproductive age diagnosed with PCOS and treated with metformin for 12 weeks, and their corresponding controls (n=41), adjusted by age and BMI. We evaluated the alteration of endocrinological and anthropometrical parameters and androgen levels. Mitochondrial O2 consumption (using a Clark-type O2 electrode), membrane potential, mitochondrial mass, and levels of reactive oxygen species (ROS) and glutathione (GSH) (by means of fluorescence microscopy) were assessed in poymorphonuclear cells. H2O2 was evaluated with the Amplex Red(R) H2O2/Peroxidase Assay kit. IL6 and TNFα were measured using the Luminex 200 flow analyser system.
RESULTS
Metformin had beneficial effects on patients by increasing mitochondrial O2 consumption, membrane potential, mitochondrial mass and glutathione levels, and by decreasing levels of reactive oxygen species and H2O2. In addition, metformin reduced glucose, follicle-stimulating hormone, IL6 and TNFα levels and increased dehydroepiandrosterone sulfate levels. HOMA-IR and mitochondrial function biomarkers positively correlated with ROS production (r=0.486, P=0.025), GSH content (r=0.710, P=0.049) and H2O2 (r=0.837, P=0.010), and negatively correlated with membrane potential (r=-0.829, P=0.011) at baseline. These differences disappeared after metformin treatment.
CONCLUSIONS
Our results demonstrate the beneficial effects of metformin treatment on mitochondrial function in leukocytes of PCOS patients.
目的
氧化应激和线粒体功能障碍与多囊卵巢综合征（PCOS）有关。本研究评估二甲双胍治疗对 PCOS 患者中性粒细胞线粒体功能的影响。此外，我们还评估了内分泌参数以及白细胞介素 6（IL6）和肿瘤坏死因子 alpha（TNFα）的水平。
设计和方法
我们的研究人群由 35 名年龄在生育期的 PCOS 患者和 41 名年龄和 BMI 相匹配的对照组组成，这些患者接受了 12 周的二甲双胍治疗。我们评估了内分泌和人体测量参数以及雄激素水平的变化。使用Clark 型 O2 电极评估多形核细胞中线粒体 O2 消耗、膜电位、线粒体质量以及活性氧（ROS）和谷胱甘肽（GSH）的水平（通过荧光显微镜）。使用 Amplex Red（R）H2O2/过氧化物酶测定试剂盒评估 H2O2。使用 Luminex 200 流式分析仪系统测量 IL6 和 TNFα。
结果
二甲双胍通过增加线粒体 O2 消耗、膜电位、线粒体质量和 GSH 水平，降低 ROS 和 H2O2 水平，对患者产生了有益的影响。此外，二甲双胍降低了葡萄糖、卵泡刺激素、IL6 和 TNFα 水平，增加了硫酸脱氢表雄酮的水平。HOMA-IR 和线粒体功能生物标志物与 ROS 产生（r=0.486，P=0.025）、GSH 含量（r=0.710，P=0.049）和 H2O2（r=0.837，P=0.010）呈正相关，与膜电位（r=-0.829，P=0.011）呈负相关。这些差异在接受二甲双胍治疗后消失。
结论
我们的结果表明，二甲双胍治疗对 PCOS 患者白细胞线粒体功能有有益的影响。
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