脑源性神经营养因子在子宫内膜异位症及其相关疼痛中的研究进展

doi:10.12280/gjfckx.20200799

摘要/Abstract

摘要：

子宫内膜异位症（EMs）是一种常见且影响广大育龄期女性的妇科良性疾病,该病的早期诊断和治疗是目前临床工作中亟需解决的难题。EMs有3种公认的病理类型,分别是腹膜型、卵巢型及深部浸润型。然而不论哪种病理类型,疼痛都是EMs患者最为突出的临床表现,包括经期腹痛、慢性盆腔痛及性交痛等不适,严重影响女性的身心健康,并增加经济负担。脑源性神经营养因子（BDNF）是神经营养蛋白家族的成员之一,不仅广泛分布于中枢和外周神经系统内,且在女性生殖系统中的分布范围也较广,在炎症反应、肿瘤的发生发展、促进神经血管生成等多种病理生理学过程中发挥重要作用。BDNF同时也是各种慢性疾病疼痛形成和维持的重要调节因子,在EMs患者的血清及组织中已发现其明显高表达,逐渐成为EMs研究的热点。

关键词: 子宫内膜异位症, 脑源性神经营养因子, 疼痛, 细胞增殖, 新生血管化,生理性

Abstract:

Endometriosis (EMs) is a common gynecological benign disease that affects the majority of women of childbearing age. The early diagnosis and treatment of EMs is an urgent problem in clinical work. There are three recognized pathological types of EMs: peritoneal type, ovarian type and deep invasive type. However, regardless of the pathological type, pain is the most prominent clinical manifestation of EMs patients, including menstrual abdominal pain, chronic pelvic pain and sexual intercourse pain, which seriously affects women′s physical and mental health and increases economic burden. Brain derived neurotrophic factor (BDNF) is one of the members of the neurotrophic protein family. It is not only widely distributed in the central and peripheral nervous system, but also widely distributed in the female reproductive system. It plays an important role in many pathophysiological processes, such as inflammatory reaction, tumor development, neuroangiogenesis and so on. BDNF is also an important regulator of pain formation and maintenance in various chronic diseases. It has been found that BDNF is highly expressed in serum and tissues of patients with EMs, and has gradually become a hot spot in EMs research.

Key words: Endometriosis, Brain-derived neurotrophic factor, Pain, Cell proliferation, Neovascularization,physiologic

李金铭, 王琳. 脑源性神经营养因子在子宫内膜异位症及其相关疼痛中的研究进展[J]. 国际妇产科学杂志, 2021, 48(3): 281-285.

LI Jin-ming, WANG Lin. Research Progress of BDNF in Endometriosis and Related Pain[J]. Journal of International Obstetrics and Gynecology, 2021, 48(3): 281-285.

参考文献 42

[1]	Zondervan KT, Becker CM, Missmer SA. Endometriosis[J]. N Engl J Med, 2020,382(13):1244-1256. doi: 10.1056/NEJMra1810764. doi: 10.1056/NEJMra1810764
[2]	Sieberg CB, Lunde CE, Borsook D. Endometriosis and pain in the adolescent- striking early to limit suffering: A narrative review[J]. Neurosci Biobehav Rev, 2020,108:866-876. doi: 10.1016/j.neubiorev.2019.12.004. doi: 10.1016/j.neubiorev.2019.12.004
[3]	洪玮, 段华, 汪沙. 脑源性神经营养因子与受体在子宫内膜异位症发生发展及相关症状中作用的研究进展[J]. 中国计划生育和妇产科, 2017,9(3):27-30,38. doi: 10.3969/j.issn.1674-4020.2017. 03.06. doi: 10.3969/j.issn.1674-4020.2017. 03.06
[4]	Chapron C, Marcellin L, Borghese B, et al. Rethinking mechanisms, diagnosis and management of endometriosis[J]. Nat Rev Endocrinol, 2019,15(11):666-682. doi: 10.1038/s41574-019-0245-z. doi: 10.1038/s41574-019-0245-z
[5]	Laganà AS, Vitale SG, Salmeri FM, et al. Unus pro omnibus, omnes pro uno: A novel, evidence-based, unifying theory for the pathogenesis of endometriosis[J]. Med Hypotheses, 2017,103:10-20. doi: 10.1016/j.mehy.2017.03.032. doi: 10.1016/j.mehy.2017.03.032
[6]	王亚楠, 陈秀娟, 李雪玲, 等. 子宫内膜干细胞研究进展[J]. 中华妇产科杂志, 2015,50(10):798-800. doi: 10.3760/cma.j.issn.0529-567x.2015.10.021. doi: 10.3760/cma.j.issn.0529-567x.2015.10.021
[7]	Gajbhiye R, McKinnon B, Mortlock S, et al. Genetic Variation at Chromosome 2q13 and Its Potential Influence on Endometriosis Susceptibility Through Effects on the IL-1 Family[J]. Reprod Sci, 2018,25(9):1307-1317. doi: 10.1177/1933719118768688. doi: 10.1177/1933719118768688 pmid: 29669463
[8]	McKinnon BD, Bertschi D, Bersinger NA, et al. Inflammation and nerve fiber interaction in endometriotic pain[J]. Trends Endocrinol Metab, 2015,26(1):1-10. doi: 10.1016/j.tem.2014.10.003. doi: 10.1016/j.tem.2014.10.003
[9]	Wei Y, Liang Y, Lin H, et al. Autonomic nervous system and inflammation interaction in endometriosis-associated pain[J]. J Neuroinflammation, 2020,17(1):80. doi: 10.1186/s12974-020-01752-1. doi: 10.1186/s12974-020-01752-1
[10]	Chen P, Wang DB, Liang YM. Evaluation of estrogen in endometriosis patients: Regulation of GATA-3 in endometrial cells and effects on Th2 cytokines[J]. J Obstet Gynaecol Res, 2016,42(6):669-677. doi: 10.1111/jog.12957. doi: 10.1111/jog.12957
[11]	Liang Y, Xie H, Wu J, et al. Villainous role of estrogen in macrophage-nerve interaction in endometriosis[J]. Reprod Biol Endocrinol, 2018,16(1):122. doi: 10.1186/s12958-018-0441-z. doi: 10.1186/s12958-018-0441-z
[12]	Ahn SH, Khalaj K, Young SL, et al. Immune-inflammation gene signatures in endometriosis patients[J]. Fertil Steril, 2016, 106(6):1420-1431.e7. doi: 10.1016/j.fertnstert.2016.07.005. doi: 10.1016/j.fertnstert.2016.07.005
[13]	Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain[J]. EMBO J, 1982,1(5):549-553. pmid: 7188352
[14]	Nijs J, Meeus M, Versijpt J, et al. Brain-derived neurotrophic factor as a driving force behind neuroplasticity in neuropathic and central sensitization pain: a new therapeutic target?[J]. Expert Opin Ther Targets, 2015,19(4):565-576. doi: 10.1517/14728222.2014.994506. doi: 10.1517/14728222.2014.994506
[15]	Zanin JP, Unsain N, Anastasia A. Growth factors and hormones pro-peptides: the unexpected adventures of the BDNF prodomain[J]. J Neurochem, 2017,141(3):330-340. doi: 10.1111/jnc.13993. doi: 10.1111/jnc.13993
[16]	Lima Giacobbo B, Doorduin J, Klein HC, et al. Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation[J]. Mol Neurobiol, 2019,56(5):3295-3312. doi: 10.1007/s12035-018-1283-6. doi: 10.1007/s12035-018-1283-6
[17]	Amadio P, Porro B, Sandrini L, et al. Patho- physiological role of BDNF in fibrin clotting[J]. Sci Rep, 2019,9(1):389. doi: 10.1038/s41598-018-37117-1. doi: 10.1038/s41598-018-37117-1
[18]	Chacón-Fernández P, Säuberli K, Colzani M, et al. Brain-derived Neurotrophic Factor in Megakaryocytes[J]. J Biol Chem, 2016,291(19):9872-9881. doi: 10.1074/jbc.M116.720029. doi: 10.1074/jbc.M116.720029
[19]	Wessels JM, Kay VR, Leyland NA, et al. Assessing brain-derived neurotrophic factor as a novel clinical marker of endometriosis[J]. Fertil Steril, 2016, 105(1):119-128.e1-5. doi: 10.1016/j.fertnstert.2015.09.003. doi: 10.1016/j.fertnstert.2015.09.003
[20]	Dong F, Zhang Q, Kong W, et al. Regulation of endometrial cell proliferation by estrogen-induced BDNF signaling pathway[J]. Gynecol Endocrinol, 2017,33(6):485-489. doi: 10.1080/09513590. 2017.1295439. doi: 10.1080/09513590. 2017.1295439
[21]	Santulli P, Marcellin L, Tosti C, et al. MAP kinases and the inflammatory signaling cascade as targets for the treatment of endometriosis?[J]. Expert Opin Ther Targets, 2015,19(11):1465-1483. doi: 10.1517/14728222.2015.1090974. doi: 10.1517/14728222.2015.1090974
[22]	Bai H, Li H, Li W, et al. The PI3K/AKT/mTOR pathway is a potential predictor of distinct invasive and migratory capacities in human ovarian cancer cell lines[J]. Oncotarget, 2015,6(28):25520-25532. doi: 10.18632/oncotarget.4550. doi: 10.18632/oncotarget.4550
[23]	Serra-Millàs M. Are the changes in the peripheral brain-derived neurotrophic factor levels due to platelet activation?[J]. World J Psychiatry, 2016,6(1):84-101. doi: 10.5498/wjp.v6.i1.84. doi: 10.5498/wjp.v6.i1.84 pmid: 27014600
[24]	Pius-Sadowska E, Machaliński B. BDNF-A key player in cardiovascular system[J]. J Mol Cell Cardiol, 2017,110:54-60. doi: 10.1016/j.yjmcc.2017.07.007. doi: 10.1016/j.yjmcc.2017.07.007
[25]	Meng L, Liu B, Ji R, et al. Targeting the BDNF/TrkB pathway for the treatment of tumors[J]. Oncol Lett, 2019,17(2):2031-2039. doi: 10.3892/ol.2018.9854. doi: 10.3892/ol.2018.9854
[26]	洪玮, 段华, 汪沙, 等. BDNF及TrKB在子宫内膜异位症在位内膜和异位病灶组织中的表达及意义[J]. 中国计划生育和妇产科, 2018,10(3):32-36. doi: 10.3969/j.issn.1674-4020.2018.03.10. doi: 10.3969/j.issn.1674-4020.2018.03.10
[27]	Falcone T, Flyckt R. Clinical Management of Endometriosis[J]. Obstet Gynecol, 2018,131(3):557-571. doi: 10.1097/AOG.0000000000002469. doi: 10.1097/AOG.0000000000002469
[28]	Soliman AM, Taylor HS, Bonafede M, et al. Incremental direct and indirect cost burden attributed to endometriosis surgeries in the United States[J]. Fertil Steril, 2017,107(5):1181-1190.e2. doi: 10.1016/j.fertnstert.2017.03.020. doi: 10.1016/j.fertnstert.2017.03.020
[29]	Kobayashi H, Yamada Y, Morioka S, et al. Mechanism of pain generation for endometriosis-associated pelvic pain[J]. Arch Gynecol Obstet, 2014,289(1):13-21. doi: 10.1007/s00404-013-3049-8. doi: 10.1007/s00404-013-3049-8
[30]	Ding S, Zhu L, Tian Y, et al. P2X3 receptor involvement in endometriosis pain via ERK signaling pathway[J]. PLoS One, 2017,12(9):e0184647. doi: 10.1371/journal.pone.0184647. doi: 10.1371/journal.pone.0184647
[31]	Bohonyi N, Pohóczky K, Szalontai B, et al. Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis[J]. Mol Pain, 2017,13:1744806917705564. doi: 10.1177/ 1744806917705564. doi: 10.1177/ 1744806917705564
[32]	McAllister SL, Giourgas BK, Faircloth EK, et al. Prostaglandin levels, vaginal innervation, and cyst innervation as peripheral contributors to endometriosis-associated vaginal hyperalgesia in rodents[J]. Mol Cell Endocrinol, 2016,437:120-129. doi: 10.1016/j.mce.2016.08.017. doi: 10.1016/j.mce.2016.08.017
[33]	Yan D, Liu X, Guo SW. Nerve fibers and endometriotic lesions: partners in crime in inflicting pains in women with endometriosis[J]. Eur J Obstet Gynecol Reprod Biol, 2017,209:14-24. doi: 10.1016/j.ejogrb.2016.06.017. doi: 10.1016/j.ejogrb.2016.06.017
[34]	Laganà AS, La Rosa VL, Rapisarda A, et al. Anxiety and depression in patients with endometriosis: impact and management challenges[J]. Int J Womens Health, 2017,9:323-330. doi: 10.2147/IJWH.S119729. doi: 10.2147/IJWH.S119729
[35]	As-Sanie S, Kim J, Schmidt-Wilcke T, et al. Functional Connectivity is Associated With Altered Brain Chemistry in Women With Endometriosis-Associated Chronic Pelvic Pain[J]. J Pain, 2016,17(1):1-13. doi: 10.1016/j.jpain.2015.09.008. doi: 10.1016/j.jpain.2015.09.008 pmid: 26456676
[36]	Sikandar S, Minett MS, Millet Q, et al. Brain-derived neurotrophic factor derived from sensory neurons plays a critical role in chronic pain[J]. Brain, 2018,141(4):1028-1039. doi: 10.1093/brain/awy009. doi: 10.1093/brain/awy009 pmid: 29394316
[37]	Ding S, Zhu T, Tian Y, et al. Role of Brain-Derived Neurotrophic Factor in Endometriosis Pain[J]. Reprod Sci, 2018,25(7):1045-1057. doi: 10.1177/1933719117732161. doi: 10.1177/1933719117732161
[38]	Zheng P, Zhang W, Leng J, et al. Research on central sensitization of endometriosis-associated pain: a systematic review of the literature[J]. J Pain Res, 2019,12:1447-1456. doi: 10.2147/JPR.S197667. doi: 10.2147/JPR.S197667 pmid: 31190954
[39]	Yu X, Ren H, Liu T, et al. Expression and significance of ERβ and TrkB in endometriosis[J]. Clin Exp Obstet Gynecol, 2016,43(1):75-81.
[40]	Stefani LC, Leite FM, da Graça L Tarragó M, et al. BDNF and serum S100B levels according the spectrum of structural pathology in chronic pain patients[J]. Neurosci Lett, 2019,706:105-109. doi: 10.1016/j.neulet.2019.05.021. doi: 10.1016/j.neulet.2019.05.021
[41]	López-Pérez AE, Nurgali K, Abalo R. Painful neurotrophins and their role in visceral pain[J]. Behav Pharmacol, 2018,29(2 and 3-Spec Issue):120-139. doi: 10.1097/FBP.0000000000000386. doi: 10.1097/FBP.0000000000000386 pmid: 29543647
[42]	Qin X, Liu Y, Feng Y, et al. Ginsenoside Rf alleviates dysmenorrhea and inflammation through the BDNF-TrkB-CREB pathway in a rat model of endometriosis[J]. Food Funct, 2019,10(1):244-249. doi: 10.1039/c8fo01839a. doi: 10.1039/c8fo01839a