全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

二甲双胍治疗子宫内膜异位症的研究进展
Advances in Metformin for Treatment of En-dometriosis

DOI: 10.12677/ACM.2023.1381807, PP. 12894-12902

Keywords: 子宫内膜异位症,二甲双胍,机制,适应症
Endometriosis
, Metformin, Mechanism, Indication

Full-Text   Cite this paper   Add to My Lib

Abstract:

子宫内膜异位症的定义是子宫腔外存在子宫内膜样组织,发病人群多为育龄期女性,发病机制复杂,临床表现异质性大,早期诊断和治疗存在困难。目前治疗方式多为激素类药物及手术,均存在一定的副作用及局限性,长期应用药物所带来的不良反应及安全性问题不容忽视,治疗效果更特异,副作用小,安全性好的药物需要发掘。二甲双胍是一种胰岛素增敏剂,在临床研究、体内、体外实验中均显示可缩小子宫内膜异位症病灶、改善患者疼痛症状及子宫内膜容受性,提升生育力。其机制主要为抗炎、抗血管增殖、抑制黏附侵袭、调节细胞间通讯、增殖和分化等,此外,二甲双胍还可影响异位子宫内膜间充质干细胞异常的自我更新能力,从干细胞水平调节异常增殖。因此,二甲双胍可能成为临床治疗子宫内膜异位症的潜在治疗选择。
Endometriosis is defined as the presence of endometrium-like tissue outside the uterus, which af-fects mostly women of childbearing age. Because of complex pathogenesis and heterogeneous clini-cal manifestations, there are many difficulties in early diagnosis and treatment. At present, most of the treatment methods are hormonal drugs and surgeries, which have certain side effects and limi-tations. The adverse reactions and safety problems caused by long-term application of drugs should not be ignored. Drugs with more specific therapeutic effects, fewer side effects and good safety pro-file need to be discovered. Metformin, an insulin sensitizer, has been shown to shrink endometriosis lesions and improve patients’ pain symptoms and endometrial tolerance, enhancing fertility in en-dometriosis patients in clinical studies, vivo and vitro experiments, by exerting anti-inflammatory, anti-vascular proliferation, inhibiting adhesion and invasion, regulating intercellular communica-tion, proliferation and differentiation, etc. In addition, metformin can affect the abnormal self-renewal ability of ectopic endometrial mesenchymal stem cells and regulate the abnormal pro-liferation from the stem cell level. Therefore, metformin may be a potential therapeutic option for the clinical treatment of endometriosis.

References

[1]  Zondervan, K.T., Becker, C.M. and Missmer, S.A. (2020) Endometriosis. New England Journal of Medicine, 382, 1244-1256.
https://doi.org/10.1056/NEJMra1810764
[2]  Simoens, S., Dunselman, G., Dirksen, C., et al. (2012) The Burden of Endometriosis: Costs and Quality of Life of Women with Endometriosis and Treated in Referral Centres. Human Reproduction, 27, 1292-1299.
https://doi.org/10.1093/humrep/des073
[3]  中国医师协会妇产科医师分会, 中华医学会妇产科学分会子宫内膜异位症协作组. 子宫内膜异位症诊治指南(第三版) [J]. 中华妇产科杂志, 2021, 56(12): 812-824.
[4]  Cheng, J., Li, C., Ying, Y., et al. (2022) Metformin Alleviates Endometriosis and Potentiates Endometrial Receptivity via Decreas-ing VEGF and MMP9 and Increasing Leukemia Inhibitor Factor and HOXA10. Frontiers in Pharmacology, 13, Article 750208.
https://doi.org/10.3389/fphar.2022.750208
[5]  Huang, X., Xiao, L., Long, Y., et al. (2022) Comparative Proteomic Analysis Reveals Metformin Improves the Expression of Biomarkers of Endometrial Receptivity in Infertile Women with Minimal/Mild Endometriosis. Reproductive Sciences, 29, 2593-2606.
https://doi.org/10.1007/s43032-022-00869-3
[6]  Feng, Y.Y., Wang, Z. and Pang, H. (2022) Role of Metformin in Inflammation. Molecular Biology Reports, 50, 789-798.
https://doi.org/10.1007/s11033-022-07954-5
[7]  Sapmaz, T., Coskun, G., Saker, D., et al. (2022) Effects of Metformin, Letrozole and Atorvastatin on Inflammation and Apoptosis in Experimental Peritoneal and Ovarian Endome-triosis in the Rat. Pathology-Research and Practice, 235, Article ID: 153951.
https://doi.org/10.1016/j.prp.2022.153951
[8]  Jamali, N., Zal, F., Mostafavi-Pour, Z., et al. (2021) Ameliora-tive Effects of Quercetin and Metformin and Their Combination against Experimental Endometriosis in Rats. Reproduc-tive Sciences, 28, 683-692.
https://doi.org/10.1007/s43032-020-00377-2
[9]  Hu, M., Zhang, Y., Li, X., et al. (2021) TLR4-Associated IRF-7 and NFκB Signaling Act as a Molecular Link between Androgen and Metformin Activities and Cytokine Synthe-sis in the PCOS Endometrium. The Journal of Clinical Endocrinology & Metabolism, 106, 1022-1040.
https://doi.org/10.1210/clinem/dgaa951
[10]  Takehara, M., Ueda, M., Yamashita, Y., et al. (2004) Vascular Endothelial Growth Factor A and C Gene Expression in Endometriosis. Human Pathology, 35, 1369-1375.
https://doi.org/10.1016/j.humpath.2004.07.020
[11]  Li, C., Zhao, H.-L., Li, Y.-J., et al. (2021) The Expression and Significance of Leukemia Inhibitory Factor, Interleukin-6 and Vascular Endothelial Growth Factor in Chinese Pa-tients with Endometriosis. Archives of Gynecology and Obstetrics, 304, 163-170.
https://doi.org/10.1007/s00404-021-05980-5
[12]  邓娟, 贺天虎, 程明军, 曹云桂. 血管内皮生长因子及其相关miRNA在子宫内膜异位症中的研究进展[J]. 中国实用妇科与产科杂志, 2022, 38(10): 1047-1050.
[13]  Mashayekhi, P., Noruzinia, M. and Khodaverdi, S. (2022) Metformin as a Potential Agent for Modulating the Faulty Endometriotic Mesenchymal Stem Cells: A Case-Control Study. International Journal of Repro-ductive BioMedicine, 20, 861-872.
https://doi.org/10.18502/ijrm.v20i10.12270
[14]  Chen, M., Zhou, Y., Xu, H., et al. (2020) Bioinformatic Analysis Reveals the Importance of Epithelial-Mesenchymal Transition in the Development of Endometriosis. Scientific Reports, 10, Article No. 8442.
https://doi.org/10.1038/s41598-020-65606-9
[15]  Hu, M., Zhang, Y., Li, X., et al. (2020) Alterations of En-dometrial Epithelial-Mesenchymal Transition and MAPK Signalling Components in Women with PCOS Are Partially Modulated by Metformin in Vitro. Molecular Human Reproduction, 26, 312-326.
https://doi.org/10.1093/molehr/gaaa023
[16]  Shimada, H., Kohno, T., Konno, T., et al. (2021) The Roles of Tricellular Tight Junction Protein Angulin-1/Lipolysis- Stimulated Lipoprotein Receptor (LSR) in Endometriosis and Endometrioid-Endometrial Carcinoma. Cancers, 13, Article No. 6341.
https://doi.org/10.3390/cancers13246341
[17]  Mari?o, G., Niso-Santano, M., Baehrecke, E.H. and Kroemer, G. (2014) Self-Consumption: The Interplay of Autophagy and Apoptosis. Nature Reviews Molecular Cell Biology, 15, 81-94.
https://doi.org/10.1038/nrm3735
[18]  Jia, L., Huang, S., Yin, X., et al. (2018) Quercetin Suppresses the Mobility of Breast Cancer by Suppressing Glycolysis through Akt-mTOR Pathway Mediated Autophagy Induction. Life Sciences, 208, 123-130.
https://doi.org/10.1016/j.lfs.2018.07.027
[19]  Wang, Q.-Q., Guo, X.-C., Li, L., Gao, Z.-H. and Ji, M. (2020) Treatment with Metformin and Sorafenib Alleviates Endometrial Hyperplasia in Polycystic Ovary Syndrome by Promot-ing Apoptosis via Synergically Regulating Autophagy. Journal of Cellular Physiology, 235, 1339-1348.
https://doi.org/10.1002/jcp.29051
[20]  Tang, G., Guo, J., Zhu, Y., et al. (2018) Metformin Inhibits Ovarian Cancer via Decreasing H3K27 Trimethylation. International Journal of Oncology, 52, 1899-1911.
https://doi.org/10.3892/ijo.2018.4343
[21]  Mu, N., Xu, T., Gao, M., et al. (2020) Therapeutic Effect of Met-formin in the Treatment of Endometrial Cancer. Oncology Letters, 20, Article No. 156.
https://doi.org/10.3892/ol.2020.12017
[22]  Zhou, Y., Xu, J.N., Zeng, C., et al. (2015) Metformin Suppresses Prostaglandin E2-Induced Cytochrome P450 Aromatase Gene Expression and Activity via Stimulation of AMP-Activated Protein Kinase in Human Endometriotic Stromal Cells. Reproductive Sciences, 22, 1162-1170.
https://doi.org/10.1177/1933719115590664
[23]  Zhuo, Z., Wang, A. and Yu, H. (2016) Metformin Targeting Autophagy Overcomes Progesterone Resistance in Endometrial Carcinoma. Archives of Gynecology and Obstetrics, 294, 1055-1061.
https://doi.org/10.1007/s00404-016-4148-0
[24]  Wu, M., Xu, H., Liu, J., et al. (2021) Metformin and Fibrosis: A Review of Existing Evidence and Mechanisms. Journal of Diabetes Research, 2021, Article ID: 6673525.
https://doi.org/10.1155/2021/6673525
[25]  McCloskey, C.W., Cook, D.P., Kelly, B.S., et al. (2020) Metfor-min Abrogates Age-Associated Ovarian Fibrosis. Clinical Cancer Research, 26, 632-642.
https://doi.org/10.1158/1078-0432.CCR-19-0603
[26]  Bernacchioni, C., Capezzuoli, T., Vannuzzi, V., et al. (2021) Sphingosine 1-Phosphate Receptors Are Dysregulated in Endometriosis: Possible Implication in Transforming Growth Factor β-Induced Fibrosis. Fertility and Sterility, 115, 501-511.
https://doi.org/10.1016/j.fertnstert.2020.08.012
[27]  Hart, P.C., Chiyoda, T., Liu, X., et al. (2019) SPHK1 Is a Novel Target of Metformin in Ovarian Cancer. Molecular Cancer Research, 17, 870-881.
https://doi.org/10.1158/1541-7786.MCR-18-0409
[28]  Oner, G., Ozcelik, B., Ozgun, M.T., et al. (2010) The Effects of Metformin and Letrozole on Endometriosis and Comparison of the Two Treatment Agents in a Rat Model. Human Reproduction, 25, 932-937.
https://doi.org/10.1093/humrep/deq016
[29]  Yari, S., Khoei, H.H., Saber, M., et al. (2021) Metformin Attenuates Expression of Angiogenic and Inflammatory Genes in Human Endometriotic Stromal Cells. Experimental Cell Research, 404, Article ID: 112659.
https://doi.org/10.1016/j.yexcr.2021.112659
[30]  Zhang, H., Xue, J., Li, M., et al. (2015) Metformin Regulates Stromal-Epithelial Cells Communication via Wnt2/β-Catenin Signaling in Endometriosis. Molecular and Cellular Endo-crinology, 413, 61-65.
https://doi.org/10.1016/j.mce.2015.06.011
[31]  Xu, J.-N., Zeng, C., Zhou, Y., et al. (2014) Metformin Inhibits StAR Expression in Human Endometriotic Stromal Cells via AMPK-MEDIATED DISRUPTIon of CREB-CRTC2 Complex Formation. The Journal of Clinical Endocrinology & Metabolism, 99, 2795-2803.
https://doi.org/10.1210/jc.2014-1593
[32]  Huang, Q., Liu, X. and Guo, S.W. (2022) Changing Prostaglandin E2 (PGE2) Signaling during Lesional Progression and Exacerbation of Endometriosis by Inhibition of PGE2 Receptor EP2 and EP4. Reproductive Medicine and Biology, 21, e12426.
https://doi.org/10.1002/rmb2.12426
[33]  蔡文娟, 樊春红. 地屈孕酮联合二甲双胍治疗子宫内膜异位症临床疗效及对患者血清FSH、LH、E2水平的影响[J]. 中国现代医药杂志, 2021, 23(10): 51-54.
[34]  Foda, A.A. and Aal, I.A.A. (2012) Metformin as A New Therapy for Endometri-osis, Its Effects on Both Clinical Picture and Cytokines Profile. Middle East Fertility Society Journal, 17, 262-267.
https://doi.org/10.1016/j.mefs.2012.09.001
[35]  Yerevanian, A. and Soukas, A.A. (2019) Metformin: Mechanisms in Human Obesity and Weight Loss. Current Obesity Reports, 8, 156-164.
https://doi.org/10.1007/s13679-019-00335-3
[36]  Morin-Papunen, L., Rantala, A.S., Unkila-Kallio, L., et al. (2012) Metformin Improves Pregnancy and Live-Birth Rates in Women with Polycystic Ovary Syndrome (PCOS): A Multicen-ter, Double-Blind, Placebo-Controlled Randomized Trial. The Journal of Clinical Endocrinology & Metabolism, 97, 1492-1500.
https://doi.org/10.1210/jc.2011-3061
[37]  Holdsworth-Carson, S.J., Dior, U.P., Colgrave, E.M., et al. (2018) The Association of Body Mass Index with Endometriosis and Disease Severity in Women with Pain. Journal of Endometrio-sis and Pelvic Pain Disorders, 10, 79-87.
https://doi.org/10.1177/2284026518773939

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133