Elia E, Sander V, Luchetti C G, Solano M E, Di Girolamo G, Gonzalez C, Motta A B
Laboratorio de Fisio-patología Ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina (UBA), Consejo de Investigaciones Científicas y Tecnológicas (CONICET), Paraguay 2155, 1121 Buenos Aires, Argentina.
Mol Hum Reprod. 2006 Aug;12(8):475-81. doi: 10.1093/molehr/gal057. Epub 2006 Jun 29.
The aim of this study was to investigate the mechanisms by which N,N'-dimethylbiguanide metformin (50 mg/100 g body weight (BW) in 0.05 ml of water, given orally with a cannula) prevents the ovarian disorders provoked by the hyperandrogenization with dehydroepiandrosterone (DHEA) in prepuberal BALB/c mice. The injection of DHEA (6 mg/100 g BW in 0.1 ml of oil) for 20 consecutive days re-creates a mouse model that resembles some aspects of the human polycystic ovary syndrome (PCOS). The treatment with DHEA increased ovarian oxidative stress because it enhanced lipid peroxidation (LPO) and diminished both catalase (CAT) activity and glutathione (GSH) content. Therefore, the treatment with DHEA diminished both ovarian nitric oxide synthase (NOS) activity and prostaglandin E (PGE) production. When metformin was administered together with DHEA, the ovarian GSH content, NOS activity and PGE production did not differ when compared with controls. However, metformin was not able to prevent the effect of DHEA on ovarian LPO or CAT activity. Finally, DHEA increased the ovarian protein expressions of inducible NOS (iNOS), inducible cyclooxygenase (COX2) and the phosphorylated AMP-dependent kinase alpha (AMPK-alpha) (Thr172). Metformin administered together with DHEA was able to prevent the increase of ovarian iNOS and COX2 expressions and to enhance the activation of phosphorylated AMPK-alpha expression.
本研究的目的是探究N，N'-二甲基双胍二甲双胍（以0.05 ml水溶解，50 mg/100 g体重，经套管口服给药）预防青春期前BALB/c小鼠因脱氢表雄酮（DHEA）雄激素化过度引发的卵巢疾病的机制。连续20天注射DHEA（6 mg/100 g体重，溶于0.1 ml油中）可重建一个类似于人类多囊卵巢综合征（PCOS）某些方面的小鼠模型。DHEA治疗增加了卵巢氧化应激，因为它增强了脂质过氧化（LPO），并降低了过氧化氢酶（CAT）活性和谷胱甘肽（GSH）含量。因此，DHEA治疗降低了卵巢一氧化氮合酶（NOS）活性和前列腺素E（PGE）的产生。当二甲双胍与DHEA一起给药时，与对照组相比，卵巢GSH含量、NOS活性和PGE产生没有差异。然而，二甲双胍无法预防DHEA对卵巢LPO或CAT活性的影响。最后，DHEA增加了卵巢中诱导型NOS（iNOS）、诱导型环氧化酶（COX2）和磷酸化的AMP依赖蛋白激酶α（AMPK-α）（Thr172）的蛋白表达。与DHEA一起给药的二甲双胍能够预防卵巢iNOS和COX2表达的增加，并增强磷酸化AMPK-α表达的激活。
