Abstract:Objective To investigate the therapeutic mechanism of Metformin on Treg cells and Th17 cells in polycystic ovary syndrome (PCOS). Methods 45 female Wister rats were gavaged by Letrozole in order to develop PCOS, and randomly chosen 5 rats to confirm the establishment of model. Then rats were divided into Metformin group [300 mg/(kg·d)], Diane group [180 mg/(kg·d)], Metformin [300 mg/(kg·d)] combined with Diane [180mg/(kg·d)] group and model group, randomly, each group had 10 rats. The other 10 female rats were arranged as control group. PCOS rats were given corresponding drugs, while control group were administrated with physiological saline, the treatment period of all groups were 28 days. The weight changes of rats weekly were observed. Ovarian histological changes were examined by Yihong-hematoxylin staining (HE). Flow cytometry was applied to delineate the phenotype of Treg cells and Th17 cells in spleen. ELISA was used to measure IL-6 and TGF-β in serum. The expression levels of Foxp3 and ROR-γt were measured by RT-PCR. Results The weight, the Treg and Th17 in spleen, Treg/Th17 ratio, the levels of IL-6 and TGF-β in serum, the expression of Foxp3 of PCOS model group were higher than control, with statistically significant difference (P < 0.05). The weight of Metformin group, Diane group and combined group were similar to control group (P > 0.05), but significantly lower than model group (P < 0.05). The cystic dilated follicle in Metformin group, Diane group and combined group decreased significantly compared with the model group. Treg cells and Th17 cells in spleen, IL-6 and transcription factor ROR-γt in serum of the Metformin group were significantly higher than the model group (P < 0.05). Th17 cells in spleen and IL-6 in serum of Diane group and the combined group were significantly lower than the model group (P < 0.05), but the expressions of transcription factor Foxp3 in ovarian tissue were significantly higher than the model group (P < 0.05). Conclusion Metformin treatment of PCOS may affect the number and proportion of Treg and Th17 cells by affecting the expression level of the serum IL-6, which can improve the microenvironment of ovarian tissue.
芦晨宇 秦培钢 杜函妤 邬海霞 古丽亚尔·艾合买提 艾丽霞 徐琦. 二甲双胍治疗多囊卵巢综合征机制研究[J]. 中国医药导报, 2017, 14(33): 17-21.
LU Chenyu QIN Peigang DU Hanyu WU Haixia Aihemaiti·Guliyaer AI Lixia XU Qi. Study on the mechanism of Metformin in the treatment of polycystic ovary syndrome. 中国医药导报, 2017, 14(33): 17-21.
[1] Jeanes YM,Reeves S. Metabolic consequences of obesity and insulin resistance in polycystic ovary syndrome:diagnostic and methodological challenges[J]. Nutr Res Rev,2017,30(1):97-105.
[2] 乔杰,李蓉,李莉,等.多囊卵巢综合征流行病学研究[J].中国实用妇科与产科杂志,2013,29(13):849-852.
[3] Yilmaz,MA,Duran C,Basaran M. The mean platelet volume and neutrophil to lymphocyte ratio in obese and lean patients with polycystic ovary syndrome [J]. J Endocrinol Invest,2016,39(1):45-53.
[4] Wu L,Li J,Xu HL,et al. IL-7/IL-7R signaling pathway might play a role in recurrent pregnancy losses by increasing inflammatory Th17 cells and decreasing Treg cells [J]. Am J Reorod Immunol,2016,76(6):454-464.
[5] 张二红,黎小妍,徐芬,等.二甲双胍改善多囊卵巢综合征大鼠胰岛素敏感性的机制[J].中山大学学报:医学科学版,2014,35(6):839-843.
[6] 王荣,羊晓勤,吕青,等.二甲双胍抗肿瘤作用机制的探讨[J].中国肿瘤临床与康复,2012,19(4):379-381.
[7] 贾莉婷,刘艳丽,马葆靖,等.两种多囊卵巢综合征大鼠模型造模方法的比较[J].郑州大学学报:医学版,2011, 46(4):538-542.
[8] Bozdag G,Mumusoglu S,Zengin D,et al. The prevalence and phenotypic features of polycystic ovary syndrome:a systematic review and meta-analysis [J]. Hum Reprod,2016,31(12):2841-2855.
[9] 刘义.多囊卵巢综合征长期管理与治疗策略[J].中国计划生育和妇产科,2014,6(6):8-11.
[10] 张二红,黎小妍,徐芬,等.二甲双胍改善多囊卵巢综合征大鼠胰岛素敏感性的机制[J].中山大学学报:医学科学版,2014,35(6):839-843.
[11] 郝翠云.达英-35和二甲双胍对多囊卵巢综合征不孕患者性激素水平及胰岛素抵抗的影响[J].中国医药导报,2016,13(9):128-130,135.
[12] Azziz R. Diagnosis of polycystic ovarian syndrome:The Rotterdam criteria are premature [J]. J Clin Endocr Metab,2006,91(3):781-785.
[13] Noack M,Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases [J]. Autoimmun Rev,2014,13(6):668-677.
[14] Krishna MB,Joseph A,Subramaniam AG,et al. Reduced Tregs in peripheral blood of PCOS patients-a consequence of aberrant II2 Signaling [J]. J Clin Endocrinol Metab,2015,100(1):282-292.
[15] 郭赛群,张颖,王丽峰,等.多囊卵巢综合征胰岛素抵抗与调节性T细胞功能的关系[J].中国妇幼健康研究,2013, 24(2):203-205.
[16] 郭葳,侯亚义,罗予.多囊卵巢综合征患者外周血中Th17和Treg细胞的改变[J].中国微生态学杂志,2014,26(7):782-785.
[17] Morikawa H,Sakaguchi S. Genetic and epigenetic basis of Treg cell development and function:from a FoxP3-centered view to an epigenome-defined view of natural Treg cells[J].Immunol Rev,2014,259(1):192-205.
[18] Skepner J,Ramesh R,Trocha M,et al. Pharmacologic Inhibition of ROR gamma t Regulates Th17 Signature Gene Expression and Suppresses Cutaneous Inflammation In Vivo [J]. J Immunol,2014,192(6):2564-2575.
[19] Joller N,Lozano E,Burkett PR,et al. Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses [J]. Immunity,2014,40(4):569-581.
[20] 黄娟,赵和平,高阳,等.老年皮肤萎缩的发病机制及对Th1/Th2细胞因子平衡的影响[J].中国老年学杂志,2017, 37(10):2504-2506.