您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报（医学版） ›› 2014, Vol. 52 ›› Issue (12): 24-29.doi: 10.6040/j.issn.1671-7554.0.2014.670

• 基础医学 • 上一篇    下一篇

胰岛素增敏剂对PCOS大鼠子宫内膜胰岛素受体底物表达的影响

王玮1, 常康2, 李晓冬3, 郝桂敏1   

  1. 1. 河北医科大学第二医院生殖科, 河北 石家庄 050000;
    2. 石家庄市第四医院生殖医学中心, 河北 石家庄 050010;
    3. 河北医科大学第二医院妇科, 河北 石家庄 050000
  • 收稿日期:2014-10-08 修回日期:2014-11-11 发布日期:2014-12-10
  • 通讯作者: 王玮。E-mail:wangwei_ivf@163.com E-mail:wangwei_ivf@163.com
  • 基金资助:
    河北省科学技术厅研究与发展计划项目科研基金 (11276103D-29)

Effect of insulin sensitizer on the expression of insulin receptor substrate in endometrium of rats with polycystic ovarian syndrome

WANG Wei1, CHANG Kang2, LI Xiaodong3, HAO Guimin1   

  1. 1. Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China;
    2. Department of Reproduction, The Forth Hospital of Shijiazhuang, Shijiazhuang 050010, Hebei, China;
    3. Department of Gynecology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
  • Received:2014-10-08 Revised:2014-11-11 Published:2014-12-10

PDF (PC)

571

摘要： 目的 探讨胰岛素增敏剂二甲双胍对多囊卵巢综合征(PCOS)大鼠子宫内膜胰岛素受体底物(IRS)1、2蛋白表达及酪氨酸磷酸化程度的影响。方法 Poretsky法建立PCOS大鼠模型,随机分为二甲双胍组和模型对照组,每组20只。空白对照组清洁级SD大鼠10只。采用免疫组织化学方法测定IRS-1和IRS-2蛋白在子宫内膜的表达及酪氨酸磷酸化程度。结果 3组大鼠子宫内膜腺上皮细胞均见IRS-1、IRS-2及酪氨酸磷酸化的表达。模型对照组子宫内膜腺上皮IRS-1、IRS-2、P-tyr(IRS-1)、P-tyr(IRS-2)表达水平明显低于空白对照组(P<0.01),二甲双胍组IRS-1、IRS-2、P-tyr(IRS-1)、P-tyr(IRS-2)表达水平显著高于模型对照组(P<0.01),低于空白对照组(P<0.05)。结论 IRS-1和IRS-2蛋白在PCOS大鼠子宫内膜表达及酪氨酸磷酸化异常与胰岛素抵抗有关;胰岛素增敏剂二甲双胍可通过增加IRS-1和IRS-2蛋白的表达水平,提高酪氨酸磷酸化程度,部分改善PCOS大鼠子宫内膜胰岛素抵抗。

关键词: 多囊卵巢综合征大鼠模型, 胰岛素受体底物, 酪氨酸磷酸化, 胰岛素抵抗, 胰岛素增敏剂

Abstract: Objective To explore the expressions of insulin receptor substrate (IRS) 1, 2 and phosphorylation of tyrosine phosphokinase in the endometrium of rats with polycystic ovarian syndrome (PCOS) after metformin treatment. Methods The PCOS models were induced by Poretsky method and randomized to the model control group (n=20) and metformin group (n=20). A total of 10 SD rats were enrolled in the blank control group. The expressions of IRS-1, 2 and phosphorylation of tyrosine phosphokinase were analyzed with immunohistochemistry. Results The expressions of IRS-1, IRS-2, P-tyr(IRS-1) and P-tyr(IRS-2) proteins in the endometrium of the metformin group were significantly higher than those of the model control group (P<0.01), but still lower than those in the blank control group (P<0.05). Conclusion There is a selective insulin resistance in the endometrium of PCOS rats, which may be related to abnormal tyrosine phosphorylation and protein expressions of insulin receptor substrates. Metformin improves tyrosine phosphorylation and protein expressions of IRS-1and IRS-2 in the endometrium and partly corrects insulin resistance.

Key words: Insulin resistance, Insulin receptor substrate, Polycystic ovarian syndrome rat model, Insulin sensitizer, Tyrosine phosphorylation

中图分类号: 

  • R711.6
[1] Sesti G, Federici M, Hribal M L, et al. Defects of the insulin receptor substrate (IRS) system in human metabolic disorders[J]. FASEB J, 2001, 15(12):2099-2111.
[2] Glintborg D, Andersen M. An update on the pathogenesis, inflammation, and metabolism in hirsutism and polycystic ovary syndrome[J]. Gynecol Endocrinol, 2010, 26(4):281-296.
[3] Cebeci F, Onsun N, Mert M. Insulin resistance in women with hirsutism[J]. Arch Med Sci, 2012, 8(2):342-346.
[4] Latrakis G, Tsionis C, Adonakis G, et al. Polycystic ovarian syndrome, insulin resistance and thickness of the endometrium[J]. Eur J Obstet Gynecol Reprod Biol, 2006, 127(2):218-221.
[5] Poretsky L, Clemons J, Bogovich K. Hyperinsulinemia and human chorionic gonadotropin synergistically promote the growth of ovarian follicular cysts in rats[J]. Metabolism, 1992, 41(8):903-910.
[6] Poretsky L, Piper B. Insulin resistance, hypersecretion of LH and a dual-defect hypothesis for the pathogenesis of polycystic ovary syndrome[J]. Obstet Gynecol, 1994, 84(4): 613-621.
[7] González F. Inflammation in Polycystic Ovary Syndrome: underpinning of insulin resistance and ovarian dysfunction[J]. Steroids, 2012, 77(4): 300-305.
[8] Diamanti-Kandarakis E, Economou F, Palimeri S. Metformin in polycystic ovary syndrome[J]. Ann N Y Acad Sci, 2010, 1205(9):192-198.
[9] Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action[J]. J Clin Invest, 2001, 108(8):1167-1174.
[10] Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications[J]. Endocr Rev, 2012, 33(6):981-1030.
[11] Siebert T I, Viola M I, Steyn D W, et al. Is metformin indicated as primary ovulation induction agent in women with PCOS? Asystematic review and Meta-analysis[J]. Gynecol Obstet Invest, 2012, 73(4): 304-313.
[12] 张添松, 邹先翔, 苏淑军, 等. 内脏脂肪素和二甲双胍对多囊卵巢综合征大鼠胰岛素抵抗和生殖内分泌的治疗作用[J]. 南方医科大学学报, 2014, 34(9): 1314-1318. ZHANG Tiansong, ZOU Xianxiang, SU Shujun, et al. Effects of visfatin and metformin on insulin resistance and reproductive endocrine in rats with polycystic ovary syndrome[J]. J South Med Univ, 2014, 34(9):1314-1318.
[1] 张媛 李英敏 冯月秋 常彩云 潘华伟 王束玫. 血清脂联素水平与肥胖、胰岛素抵抗的关系探讨[J]. 山东大学学报(医学版), 2209, 47(6): 124-.
[2] 刘淋,王晓楠,杨雅溪,王江腾,李旭,周新丽,管庆波,张栩. 甘油三酯-葡萄糖指数与颅内动脉粥样硬化性狭窄的相关性[J]. 山东大学学报 (医学版), 2024, 62(8): 93-100.
[3] 许沛晨,李晓博,庄向华,娄能俊,吕丽,周玲雁,牟亚朋,宋玉文,陈诗鸿. 儿童Alstrom综合征2例并文献复习[J]. 山东大学学报 (医学版), 2024, 62(3): 107-111.
[4] 赵美茹,朱迪,刘淋,管庆波,张栩. 简易胰岛素抵抗指标与698例2型糖尿病患者发生高尿酸血症风险的关联[J]. 山东大学学报 (医学版), 2022, 60(12): 44-51.
[5] 牛群,石婧婧,符江. WNT5A基因对卵巢颗粒细胞胰岛素反应性和胰岛素抵抗的调控作用[J]. 山东大学学报 (医学版), 2021, 59(6): 57-63.
[6] 哈灵侠,殷婷,吴阳阳,黎维霞,杜玉冬. 多囊卵巢综合征患者中胰岛素抵抗与子宫内膜局部炎症因子及葡萄糖转运蛋白-4表达的相关性[J]. 山东大学学报 (医学版), 2021, 59(11): 41-47.
[7] 徐红照,郝宗山, 沈德嫱,李朝苹,陈立勇. 核糖体蛋白S6激酶2沉默在乙醇诱导的心肌胰岛素抵抗中的作用[J]. 山东大学学报 (医学版), 2020, 58(4): 84-89.
[8] 吴成威,孙博实,周军德,蒋天明,迟强. 术前口服多糖溶液对结直肠癌患者术后胰岛素抵抗的关联性研究[J]. 山东大学学报 (医学版), 2019, 57(9): 48-53.
[9] 王敏,王春花,刘鸿丽,何志良,崔薇薇,王磊,刘杰军. 男性儿童瘦素抵抗对成年后健康状况的影响[J]. 山东大学学报 (医学版), 2018, 56(10): 114-118.
[10] 李健,徐冰,闫新峰,徐万菊,常晓天. 筛选TXNDC5与胰岛素相关信号通路关键基因的探讨[J]. 山东大学学报（医学版）, 2017, 55(3): 88-93.
[11] 李洪志,申永超,刘洁婷,赵孝金,初彦辉,袁晓环. 11β-HSD1抑制剂改善db/db小鼠胰岛素敏感性的实验研究[J]. 山东大学学报（医学版）, 2017, 55(10): 59-64.
[12] 贾月月,刘洪彬,李婧博,李敬,张江涛, 孙梅,石玉华. 多囊卵巢综合征患者颗粒细胞microRNA-200b的表达及影响[J]. 山东大学学报（医学版）, 2017, 55(1): 63-68.
[13] 李婧博,刘洪彬,贾月月,王泽,孙梅,石玉华. microRNA-183在PCOS胰岛素抵抗中的表达及其临床意义[J]. 山东大学学报（医学版）, 2017, 55(1): 69-74.
[14] 林栋,管庆波. 2型糖尿病男性患者血清睾酮水平低下对非酒精性脂肪肝的影响[J]. 山东大学学报（医学版）, 2016, 54(7): 33-37.
[15] 许艺博,季晓康,李向一,申振伟,薛付忠. 尿液pH与代谢综合征的相关性[J]. 山东大学学报（医学版）, 2016, 54(12): 82-85.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发