罗格列酮对体外培养的PCOS患者卵巢黄素化颗粒细胞胰岛素抵抗的影响

Effect of Rosiglitazone on Insulin Resistance of Ovarian Luteinizing Granulosa Cells from Patients with Polycystic Ovarian Syndrome in Vitro

目的:探讨罗格列酮改善PCOS卵巢局部胰岛素抵抗的作用。方法:收集行IVF-ET治疗的11例PCOS患者(PCOS组)和15例排卵正常的输卵管性不孕患者(对照组)促排卵后黄素化颗粒细胞行体外培养,分别用不同浓度罗格列酮(0nmol/L、1nmol/L、10nmol/L、100nmol/L、1000nmol/L、10000nmol/L)处理细胞48h,采用RT-PCR和Westernblotting分别检测卵巢黄素化颗粒细胞胰岛素受体底物(IRS)-1和IRS-2mRNA的表达及蛋白含量。结果:①基础状态下,PCOS组IRS-1mRNA表达及蛋白含量较对照组显著增加;IRS-2mRNA表达及蛋白含量较对照组显著降低(P<0.05);②不同浓度罗格列酮作用后,PCOS组IRS-1mRNA及蛋白表达显著降低,IRS-2mRNA及蛋白表达显著增加,并呈剂量依赖性,而正常对照组无变化。结论:PCOS患者卵巢局部存在胰岛素抵抗,其原因可能与IRS-1和IRS-2mRNA及蛋白表达异常有关;罗格列酮可通过提高黄素化颗粒细胞IRS-2的表达,降低IRS-1的表达,改善PCOS患者卵巢局部胰岛素抵抗。

Objective： To explore molecular mechanisms of the rosiglitazone effect on ovarian lnsuhn resistance in PCOS. Methods： Cultured luteinizing granulosa cells from PCOS （n=11） and normal ovulatory （as control, n=15） were obtained in the process of IVF. By treating with differert concentrations of rosiglitazone for 48 h, the rnRNA and protein expression of insulin receptor substrates （IRS）-1, IRS-2 in ovarian luteinizing granulose cells were assessed by semi-quantitative RT-PCR and Western blotting, respectively. Results： 1） As compared with control group, IRS-1mR.NA expression and protein content were significantly increased in PCOS patients （P〈0.05）, but IRS-2 mRNA expression and protein content were decreased significantly （P〈0.05）. 2） Rosiglitazone corrected the abnormal mRNA and protein expression ofIRS-1, IRS-2 in a dose-dependent manner in PCOS group, but had no effect in control group. Conclusion： 1） There is a selective insulin resistance in ovarian luteinizing granulosa cells from patients with PCOS, the reason may be related to abnormal mRNA and protein expression of IRS. 2） Rosiglitazone improved ovarian function of PCOS, the reason may be related to corrected the abnormal mRNA and protein expression of IRS in ovarian luteinizing granulosa cells.