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) ›› 2021, Vol. 59 ›› Issue (11): 41-47.doi: 10.6040/j.issn.1671-7554.0.2021.0733

• 临床医学 • 上一篇    下一篇

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

哈灵侠1,2,殷婷1,2,吴阳阳1,2,黎维霞1,2,杜玉冬1,2   

  1. 1. 宁夏医科大学总医院生殖医学中心, 宁夏 银川 750004;2.宁夏医科大学生育力保持教育部重点实验室, 宁夏 银川 750004
  • 发布日期:2021-11-11
  • 通讯作者: 哈灵侠. E-mail:hlxny@163.com
  • 基金资助:
    宁夏自然科学基金(2019AAC03190)

Correlation between insulin resistance and expressions of local inflammatory factors and glucose transporter protein type-4 in the endometrium of patients with polycystic ovary syndrome

HA Lingxia1,2, YIN Ting1,2, WU Yangyang1,2, LI Weixia1,2, DU Yudong1,2   

  1. 1. Center for Reproductive Medicine, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China;
    2. Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia, China
  • Published:2021-11-11

PDF (PC)

135

摘要： 目的 探讨子宫内膜局部炎症因子及葡萄糖转运蛋白-4(GLUT-4)在多囊卵巢综合征(PCOS)患者子宫内膜上的表达,分析PCOS患者胰岛素抵抗与子宫内膜炎症因子及GLUT-4表达的相关性。 方法 选取2018年6月至2020年7月就诊的60例PCOS患者,根据胰岛素抵抗指数(HOMA-IR)分为PCOS胰岛素抵抗组(A组,n=30)和PCOS非胰岛素抵抗组(B组,n=30);选取同期的60例非PCOS患者作为对照,分为胰岛素抵抗组(C组,n=30)和正常对照组(D组,n=30)。检测血清卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、睾酮(T)、泌乳素(PRL)、抗苗勒氏管激素(AMH)、空腹血糖及胰岛素水平。采用免疫组化法检测4组患者子宫内膜肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)p65、GLUT-4的表达。 结果 (1)4组患者间BMI、AMH、LH、T比较,差异有统计学意义(F值分别为57.35、29.54、16.77、21.20, P<0.001))。其中,与B组相比,A组患者BMI升高;与D组相比,C组患者BMI升高。与C、D组相比,A、B两组患者血清中AMH、LH升高。A组患者血清中T高于B组;(2)4组患者间子宫内膜中NF-κB p65、TNF-α及GLUT-4的表达差异均有统计学意义(F值分别为76.90、 45.13、47.75, P<0.001)。其中,与B组相比,A组患者子宫内膜中NF-κBp65、TNF-α表达升高,而GLUT-4的表达降低。与D组相比,C组患者子宫内膜中NF-κBp65、TNF-α表达升高,而GLUT-4表达降低;(3)Logistic回归分析结果显示,在PCOS及非PCOS患者中, HOMA-IR与NF-κBp65呈正相关(P<0.05),与GLUT-4呈负相关(P<0.05)。在非PCOS患者中,HOMA-IR与BMI呈正相关(P<0.05)。 结论 PCOS患者胰岛素抵抗与NF-κBp65及GLUT-4相关,可能会导致子宫内膜局部炎症因子表达增加,GLUT-4表达降低。

关键词: 多囊卵巢综合征, 胰岛素抵抗, 核因子-κB, 肿瘤坏死因子-α, 葡萄糖转运蛋白-4

Abstract: Objective To explore the expressions of local inflammatory factors and glucose transporter protein type-4(GLUT-4)in the endometrium of patients with polycystic ovary syndrome(PCOS), and to analyze the correlation between insulin resistance(IR)and the expressions of inflammatory factors and GLUT-4. Methods A total of 60 PCOS patients treated during June 2018 and July 2020 were enrolled. Based on the homeostasis model assessment for insulin resistance index(HOMA-IR), the patients were divided into IR PCOS group(n=30)and non-IR PCOS group(n=30). Meanwhile, 60 non-PCOS patients were collected and divided into IR group(n=30)and normal control group(n=30). Follicle stimulating hormone(FSH), luteining hormone(LH), estradiol(E2), testosterone(T), prolactin(PRL)and anti-Mullerian hormone(AMH)were detected. The expressions of tumor necrosis factor alpha(TNF-α), nuclear factor-kappa B(NF-κB)and GLUT-4 in the endometrium were detected with immunohistochemistry. Results (1) There were significant differences in body mass index(BMI), AMH, LH and T among the 4 groups(F=57.35, 29.54, 16.77, 21.20, P<0.001). Group A had higher BMI than group B; group C had higher BMI than group D. Groups A and B had higher levels of AMH and LH than groups C and D. Group A had higher T than group B. (2) There were significant differences in expressions of TNF-α, NF-κBp65 and GLUT-4 among the 4 groups(F=76.90, 45.13, 47.75, P<0.001). Group A had higher expressions of TNF-α and NF-κBp65 but lower GLUT-4 than group B. Group C had higher expressions of TNF-α and NF-κBp65 but lower expression of GLUT-4 than group D. (3)The results of multivariate Logistic regression analysis showed that HOMA-IR was positively correlated with the expression of NF-κBp65 but negatively correlated with the expression of GLUT-4 in PCOS and non-PCOS patients(P<0.05); HOMA-IR was positively correlated with BMI in non-PCOS patients(P<0.05). Conclusion Insulin resistance is associated with NF-κBp65 and GLUT-4 in PCOS patients. It may increase the expressions of local inflammatory factors and decrease the expression of GLUT-4 in the endometrium.

Key words: Polycystic ovary syndrome, Insulin resistance, Nuclear factor-κB, Tumor necrosis factor-alpha, Glucose transporter protein type-4

中图分类号: 

  • R711.71
[1] Hoeger KM, Dokras A, Piltonen T. Update on PCOS: Consequences, challenges, and guiding treatment [J]. J Clin Endocrinol Metab, 2021, 106(3): e1071-e1083.
[2] Glueck CJ, Goldenberg N. Characteristics of obesity in polycystic ovary syndrome: etiology, treatment, and genetics [J]. Metabolism, 2019, 92(3): 108-120.
[3] 乔杰, 齐新宇, 徐雅兰, 等. 关注影响女性健康的重要生殖内分泌疾病多囊卵巢综合征[J]. 中国实用妇科与产科杂志, 2020, 36(1): 1-9.
[4] Bai X, Zheng L, Li D, et al. Research progress of endometrial receptivity in patients with polycystic ovary syndrome: a systematic review [J]. Reprod Biol Endocrinol, 2021, 19(1): 122. doi: 10.1186/s12958-021-00802-4.
[5] Rostamtabar M, Esmaeilzadeh S, Tourani M, et al. Pathophysiological roles of chronic low-grade inflammation mediators in polycystic ovary syndrome [J]. Cell Physiol, 2021, 236(2): 824-838.
[6] Rudnicka E, Kunicki M, Suchta K, et al. Inflammatory markers in women with polycystic ovary syndrome [J]. Biomed Res Int, 2020, 4(3): 4092470. doi: 10.1155/2020/4092470.
[7] Su CL, Chen M, Huang HY, et al. Testosterone enhances lipopolysaccharide-induced interleukin-6 and macrophage chemotactic protein-1 expression by activating the extracellular signal-regulated kinase 1/2/nuclear factor-κB signalling pathways in 3T3-L1 adipocytes [J]. Molecular Medicine Reports, 2015, 12(1): 696-704.
[8] Van Quickelberghe E, De Sutter D, van Loo G, et al. A protein-protein interaction map of the TNF-induced NF-κ B signal transduction pathway [J]. Sci Data, 2018, 18(5): 180289. doi: 10.1038/sdata.2018.289.
[9] Oróstica L, García P, Vera C, et al. Effect of TNF-α on molecules related to the insulin action in endometrial cells exposed to hyperandrogenic and hyperinsulinic conditions characteristics of polycystic ovary syndrome [J]. Reprod Sci, 2018, 25(7): 1000-1009.
[10] Jayaraman S, Devarajan N, Rajagopal P, et al. β-sitosterol circumvents obesity induced inflammation and insulin resistance by down-regulating IKKbeta/NF-kappaB and JNK signaling pathway in adipocytes of type 2 diabetic rats [J]. Molecules, 2021, 26(7): 2101. doi: 10.3390/molecules26072101.
[11] 邢小燕, 杨文英, 杨兆军. 胰岛素抵抗指数在不同糖耐量人群中诊断代谢综合征的作用[J]. 中华糖尿病杂志, 2004(3): 31-35. XING Xiaoyan, YANG Wenying, YANG Zhaojun. The diagnostic significance of homeostasis model assessment of insulin resistance in metabolic syndrome among subjects with different glucose tolerance [J]. Chinese Journal of Diabetes, 2004(3): 31-35.
[12] Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome(PCOS)[J]. Hum Reprod, 2004, 19(1): 41-47.
[13] 贺婷婷, 刘红, 舒凯云, 等. 多囊卵巢综合征患者颗粒细胞中 microRNA-141的表达与意义[J]. 山东大学学报(医学版), 2019, 57(5): 116-120. HE Tingting, LIU Hong, SHU Kaiyun, et al. Expression and significance of microRNA-141 in granulosa cells of patients with polycystic ovary syndrome [J]. Journal of Shandong University(Heart Science), 2019, 57(5): 116-120.
[14] He Y, Lu Y, Zhu Q, et al. Influence of metabolic syndrome on female fertility and in vitro fertilization outcomes in PCOS women [J].Am J Obstet Gynecol, 2019, 221(2): 138. doi: 10.1016/j.ajog.2019.03.011.
[15] Jiang NX, Li XL. The disorders of endometrial receptivity in PCOS and its mechanisms [J]. Reprod Sci, 2021, 27. doi: 10.1007/s43032-021-00629-9.
[16] Cirillo F, Catellani C, Lazzeroni P, et al. MiRNAs regulating insulin sensitivity are dysregulated in polycystic ovary syndrome(PCOS)ovaries and are associated with markers of inflammation and insulin sensitivity [J]. Front Endocrinol(Lausanne), 2019, 13(10): 879. doi: 10.3389/fendo.2019.00879.
[17] Erkan G, Tayyar AT, Acmaz G, et al. Role of osteocalcin, tumor necrosis factor-alpha and adiponectin in polycystic ovary syndrome patients with insulin resistance [J]. Turk J Obstet Gynecol, 2017, 14(2): 89-93.
[18] Gnanadass AS, Prabhu DY, Gopalakrishnan VA. Association of metabolic and inflammatory markers with polycystic ovarian syndrome(PCOS): an update [J]. Arch Gynecol Obstet, 2021, 303(3): 631-643.
[19] Koc O, Ozdemirici S, Acet M, et al. Nuclear factor-κB expression in the endometrium of normal and overweight women with polycystic ovary syndrome [J]. J Obstet Gynaecol, 2017, 37(7): 924-930.
[20] Mioni R, Chiarelli S, Xamin N, et al. Evidence for the presence of glucose transporter 4 in the endometrium and its regulation in polycystic ovary syndrome patients [J]. J Clin Endocrinol Metab, 2004, 89(8): 4089-4096.
[21] Unamuno X, Gómez-Ambrosi J, Rodríguez A, et al. Adipokine dysregulation and adipose tissue inflammation in human obesity [J]. Eur J Clin Invest, 2018, 48(9): e12997. doi: 10.1111/eci.12997.
[22] Sarkar P, Thirumurugan K. New insights into TNFα/PTP1B and PPARγ pathway through RNF213-a link between inflammation, obesity, insulin resistance, and Moyamoya disease [J]. Gene, 2021, 771(1): 145340. doi: 10.1016/j.gene.2020.145340.
[23] Jiang B, Xue M, Xu D, et al. Upregulation of micro RNA-204 improves insulin resistance of polycystic ovarian syndrome via inhibition of HMGB1 and the inactivation of the TLR4/NF-κB pathway [J]. Cell Cycle, 2020, 19(6): 697-710.
[24] Mozzanega B, Mioni R, Granzotto M, et al. Obesity reduces the expression of GLUT4 in the endometrium of normoinsulinemic women affected by the polycystic ovary syndrome [J]. Ann N Y Acad Sci, 2004, 1034(12): 364-374.
[25] Freitas WR, Oliveira LVF, Perez EA, et al. Systemic inflammation in severe obese patients undergoing surgery for obesity and weight-related diseases [J]. Obes Surg, 2018, 28(7): 1931-1942.
[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] 虎娜,孙苗,邢莎莎,许丹霞,海小明,马玲,杨丽,勉昱琛,何瑞,陈冬梅,马会明. 月见草油抵抗多囊卵巢综合征大鼠卵巢氧化应激[J]. 山东大学学报 (医学版), 2022, 60(5): 22-30.
[3] 宋甜,付琳琳,王秋敏,杨晓,王莹,边月红,石玉华. 脂肪酸转运蛋白1在多囊卵巢综合征患者颗粒细胞中的表达[J]. 山东大学学报 (医学版), 2022, 60(2): 22-26.
[4] 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.
[5] 韩笑,李雷,刘聪聪. 睾酮对于多囊卵巢综合征易感基因Tox3表达的影响[J]. 山东大学学报 (医学版), 2021, 59(4): 42-47.
[6] 宫小舒,吴日超,李秀芳,潘烨,王泽,石玉华. 603例多囊卵巢综合征患者不同促排卵内膜准备方案对冻胚移植结局的影响[J]. 山东大学学报 (医学版), 2021, 59(3): 48-54.
[7] 丁祥云,于清梅,张文芳,庄园,郝晶. 胰岛素样生长因子II在84例多囊卵巢综合征患者颗粒细胞中的表达和促排卵结局的相关性[J]. 山东大学学报 (医学版), 2020, 1(7): 60-66.
[8] 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.
[9] 宋海霞,袁彩霞,范玲玲. 体质量指数对夫精人工授精妊娠结局的影响[J]. 山东大学学报 (医学版), 2020, 58(1): 49-53.
[10] 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.
[11] 贺婷婷,刘红,舒凯云,宋晓翠,石玉华. 多囊卵巢综合征患者颗粒细胞中microRNA-141的表达与意义[J]. 山东大学学报 (医学版), 2019, 57(5): 116-120.
[12] 贺婷婷,刘昕,刘洪彬,赵世刚,张秀清,刘庆庆,游力,石玉华. 多囊卵巢综合征患者颗粒细胞叉头框蛋白O1 mRNA的表达与意义[J]. 山东大学学报 (医学版), 2019, 57(2): 75-79.
[13] 郑庆梅, 姚勤. 复方口服避孕药抑制垂体功能1例分析[J]. 山东大学学报 (医学版), 2019, 57(10): 118-119.
[14] 刘聪聪,刘洪彬,符江,李雷. 多囊卵巢综合征易感基因dennd1a在斑马鱼模型中的表达特性[J]. 山东大学学报 (医学版), 2019, 57(1): 48-54.
[15] 舒心,王群,黄涛,赵世刚,石玉华,刘洪彬. 多囊卵巢综合征高雄激素血症患者颗粒细胞FBP1基因的表达及影响[J]. 山东大学学报 (医学版), 2018, 56(4): 58-63.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 史爽,李娟,米琦,王允山,杜鲁涛,王传新. 胃癌miRNAs预后风险评分模型的构建与应用[J]. 山东大学学报 (医学版), 2020, 1(7): 47 -52 .
[2] 姜保东,马祥兴,王青,王茜,冯晓源,李克,于富华 . 脑CT静脉造影扫描时相及重建层厚的选择[J]. 山东大学学报(医学版), 2008, 46(11): 1084 -1086 .
[3] 黄飞,王怀经,邢毅,高薇,李永刚,邢子英,李振中. NGF和GM1联合应用对坐骨神经损伤大鼠初级传入神经元的保护作用[J]. 山东大学学报(医学版), 2006, 44(4): 332 -335 .
[4] 吕龙飞,李林,李树海,亓磊,鲁铭,程传乐,田辉. 腔镜下细针导管空肠造瘘在微创McKeown食管癌切除术中的应用[J]. 山东大学学报 (医学版), 2020, 1(7): 77 -81 .
[5] 邵海港, 王璇, 王青. 山东地区人下颌第一前磨牙根管系统解剖研究[J]. 山东大学学报（医学版）, 2014, 52(9): 85 -89 .
[6] 李洧,李道卫,叶茜,高顺翠,姜淑娟. 经支气管镜针吸活检在纵隔疾病诊断中的价值[J]. 山东大学学报(医学版), 2008, 46(11): 1063 -1065 .
[7] 唐芳1,2 ，张颖倩3 ，王志强4 ,康殿民4 ,王洁贞1 ,薛付忠1 . 自然疫源性疾病疫源地空间结构的二维
最小生成树模型及其应用
[J]. 山东大学学报(医学版), 2009, 47(01): 106 -110 .
[8] 王旭平,赵玲,冯玉新,商林珊,刘金成,曹伟朋,朱晓音,辛华. 绞股蓝总苷对谷氨酸诱导的胎鼠大脑皮层神经元氧化性损伤保护机制的研究[J]. 山东大学学报(医学版), 2006, 44(6): 564 -567 .
[9] 王学萍,杨洪玲. 洛汀新治疗高血压50例报告[J]. 山东大学学报(医学版), 2007, (2): 213 .
[10] 刘海春 张剑锋 陈允震. 骨质疏松大鼠股骨生物力学特性与骨胶原质量变化的相关研究[J]. 山东大学学报(医学版), 2009, 47(5): 42 -45 .
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