The new application of mifepristone in the relief of adenomyosis-caused dysmenorrhea

被引:52
作者
Che, Xuan [1 ,2 ]
Wang, Jianzhang [1 ]
He, Jiayi [1 ]
Guo, Xinyue [1 ]
Li, Tiantian [1 ]
Zhang, Xinmei [1 ]
机构
[1] Zhejiang Univ, Womens Hosp, Sch Med, Hangzhou 310006, Zhejiang, Peoples R China
[2] Jiaxing Matern & Child Hlth Care Hosp, Jiaxing 314000, Zhejiang, Peoples R China
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
adenomyosis; dysmenorrhea; mifepristone; inflammation; mast cell; nerve fiber; TUMOR-NECROSIS-FACTOR; MAST-CELLS; MEDROXYPROGESTERONE ACETATE; PELVIC PAIN; EXPRESSION; ACTIVATION; WOMEN; ENDOMETRIOSIS; HYPERALGESIA; INHIBITION;
D O I
10.7150/ijms.39252
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Background: Adenomyosis is a quite common gynecological disorder and above 30% of patients have typical secondary and progressive dysmenorrhea. Current treatments still have many disadvantages and thereby the novel treatment aiming to relieve dysmenorrhea still needs to be further investigated. Mifepristone is a wonderful drug because it is effective, safe and cheap in many diseases including adenomyosis. In this study, we aim to investigate if mifepristone could be used in the treatment of adenomyosis-associated dysmenorrhea. Methods: Human primary endometrial epithelial and stromal cells from adenomyosis patients were isolated and treated with mifepristone. RNA-sequencing was then performed to detect the gene changes of pain-related inflammatory mediators. Meanwhile, the effect of mifepristone on the infiltration and degranulation of mast cells were investigated in adenomyosis lesions. Additionally, the role of mifepristone on the density of nerve fibers was also studied in the ectopic endometrium. At last, to evaluate the therapeutic efficacy of mifepristone on dysmenorrhea of adenomyosis, twenty participants were included and the visual analog scale (VAS) score was assessed and compared before and after treatment with mifepristone. Results: We demonstrated that mifepristone reduced the secretion of IL-6 and TNF-alpha from endometrial epithelial and stromal cells, restricted the infiltration and degranulation of mast cells in eutopic and ectopic endometrium and decreased the density of nerve fibers by inhibiting the migration capacity of nerve cells in adenomyosis. Meanwhile, we found that mifepristone could significantly relieve dysmenorrhea of adenomyosis. Conclusion: The findings demonstrated that mifepristone could be applied in the treatment of dysmenorrhea for the adenomyosis patients.
引用
收藏
页码:224 / 233
页数:10
相关论文
共 41 条
[1]
Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis [J].
Anaf, V ;
Simon, P ;
El Nakadi, I ;
Fayt, I ;
Simonart, T ;
Buxant, F ;
Noel, JC .
HUMAN REPRODUCTION, 2002, 17 (07) :1895-1900
[2]
Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2 [J].
Biedermann, T ;
Kneilling, M ;
Mailhammer, R ;
Maier, K ;
Sander, CA ;
Kollias, G ;
Kunkel, SL ;
Hültner, L ;
Röcken, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (10) :1441-1451
[3]
Selective progesterone receptor modulators in reproductive medicine: pharmacology, clinical efficacy and safety [J].
Bouchard, Philippe ;
Chabbert-Buffet, Nathalie ;
Fauser, Bart C. J. M. .
FERTILITY AND STERILITY, 2011, 96 (05) :1175-1189
[4]
Expression of Inflammatory and Neurogenic Mediators in Adenomyosis: A Pathogenetic Role [J].
Carrarelli, Patrizia ;
Yen, Chih-Feng ;
Funghi, Lucia ;
Arcuri, Felice ;
Tosti, Claudia ;
Bifulco, Giuseppe ;
Luddi, Alice ;
Lee, Chyi-Long ;
Petraglia, Felice .
REPRODUCTIVE SCIENCES, 2017, 24 (03) :369-375
[5]
Clonogenicity of human endometrial epithelial and stromal cellss [J].
Chan, RWS ;
Schwab, KE ;
Gargett, CE .
BIOLOGY OF REPRODUCTION, 2004, 70 (06) :1738-1750
[6]
Possible Loss of GABAergic Inhibition in Mice With Induced Adenomyosis and Treatment With Epigallocatechin-3-Gallate Attenuates the Loss With Improved Hyperalgesia [J].
Chen, Yumei ;
Zhu, Bo ;
Zhang, Hongping ;
Ding, Ding ;
Liu, Xishi ;
Guo, Sun-Wei .
REPRODUCTIVE SCIENCES, 2014, 21 (07) :869-882
[7]
Targeting mast cells in endometriosis with Janus kinase 3 inhibitor, JANEX-1 [J].
D'Cruz, Osmond J. ;
Uckun, Fatih M. .
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 2007, 58 (02) :75-97
[8]
Remodeling of estrogen-dependent sympathetic nerve fibers seems to be disturbed in adenomyosis [J].
de Arellano, Maria L. Barcena ;
Oldeweme, Jeannette ;
Arnold, Julia ;
Schneider, Achim ;
Mechsner, Sylvia .
FERTILITY AND STERILITY, 2013, 100 (03) :801-+
[9]
Role of Brain-Derived Neurotrophic Factor in Endometriosis Pain [J].
Ding, Shaojie ;
Zhu, Tianhong ;
Tian, Yonghong ;
Xu, Ping ;
Chen, Zhengyun ;
Huang, Xiufeng ;
Zhang, Xinmei .
REPRODUCTIVE SCIENCES, 2018, 25 (07) :1045-1057
[10]
Mast Cells and Neuroinflammation [J].
Dong, Hongquan ;
Zhang, Xiang ;
Qian, Yanning .
MEDICAL SCIENCE MONITOR BASIC RESEARCH, 2014, 20 :200-206