Effect of Different Therapeutic Regimens of Mifepristone on the Expression of Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Endometriotic Rats_West China Medical Journal

Authors：

YANG Lin , XIONG Ying , QIAO Lin , CAI Linrui , HU Yuling , ZHONG Lanping ,  XU Kehui.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

XU Kehui., Email: yang1lin@163.com

Keywords：

米非司酮; 子宫内膜异位症; 大鼠; 基质金属蛋白酶-9; 基质金属蛋白酶组织特异性抑制物-1

DOI：

10.7507/1002-0179.20130275

Video：

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目的　探讨不同剂量和不同疗程米非司酮对大鼠子宫异位内膜基质金属蛋白酶-9（MMP-9）及其组织特异性抑制物-1（TIMP-1）表达的影响。方法　65只子宫内膜异位症大鼠随机分为低剂量组、高剂量组、对照组。各个剂量组分别灌胃20、30、40 d后取异位子宫内膜组织用免疫组织化学法检测MMP-9及TIMP-1的表达，并计算MMP-9/TIMP-1比值。结果　低剂量组和高剂量组均能使异位内膜MMP-9表达下降（P＜0.05）,TIMP-1表达升高（P＜0.05）,高剂量组的作用更加明显，与低剂量组差异有统计学意义（P＜0.05）；用药30 d低剂量组TIMP-1表达最高，与用药20 d和40 d相比差异有统计学意义（P＜0.05）,同样高剂量组用药30d TIMP-1的表达也最高，与用药20 d和用药40 d比较差异有统计学意义（P＜0.05）。与用药20、40 d比较差异有统计学意义（P＜0.05）。结论　米非司酮能够降低大鼠异位子宫内膜的侵袭能力，高剂量米非司酮抑制效果更明显；用药30 d米非司酮对大鼠异位内膜的侵袭能力抑制最强，延长用药时间不能使异位内膜侵袭能力继续下降。

Citation： YANG Lin,XIONG Ying,QIAO Lin,CAI Linrui,HU Yuling,ZHONG Lanping,XU Kehui.. Effect of Different Therapeutic Regimens of Mifepristone on the Expression of Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Endometriotic Rats. West China Medical Journal, 2013, 28(6): 879-883. doi: 10.7507/1002-0179.20130275 Copy

1.	郎景和. 子宫内膜异位症研究的任务与展望(之一)[J]. 中华妇产科杂志, 2006, 41(5): 289-290.
2.	Kettel LM, Murphy AA, Mortola JF, et al. Endocrine responses to long-term administration of the antiprogesterone RU486 in patients with pelvic endometriosis[J]. Fertil Steril, 1991, 56(3): 402-407.
3.	张曦, 王鑫, 王红静, 等. 大鼠子宫内膜异位症模型建立方法的探索[J]. 华西医学, 2007, 22(4): 831-833.
4.	刘万里, 薛茜, 曹明芹, 等. 用SPSS实现完全随机设计多组比较秩和检验的多重比较[J]. 地方病通报, 2007, 22(2): 27-29.
5.	Melin A, Sparén P, Persson I, et al. Endometriosis and the risk of Cancer with special emphasis on ovarian Cancer[J]. Hum Reprod, 2006, 21(5): 1237-1242.
6.	邬巧霞. 腹腔镜手术联合米非司酮治疗子宫内膜异位症的临床研究[J]. 中国妇幼保健, 2010, 25(23): 3355-3356.
7.	周夏伶, 许剑利, 乔林, 等. 米非司酮治疗子宫内膜异位症临床效果观察[J]. 中国计划生育学杂志, 2009, 159(1): 36-38.
8.	Sidell N, Han SW, Parthasarathy S. Regulation and modulation of abnormal immune responses in endometriosis[J]. Ann N Y Acad Sci, 2002, 955: 159-173.
9.	Li X, Bao Y, Fang P, et al. Effect of mifepristone on COX-2 both in eutopic and ectopic endometrium in mouse endometriotic model[J]. Arch Gynecol Obstet, 2012, 286(4): 939-946.
10.	Di Carlo A. Matrix metalloproteinase-2 and -9 in the sera and in the urine of human oncocytoma and renal cell carcinoma[J]. Oncol Rep, 2012, 28(3): 1051-1056.
11.	Reis ST, Leite KR, Piovesan LF, et al. Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer[J]. BMC Urol, 2012, 12: 18.
12.	Nap AW, Dunselman GA, de Goeij AF, et al. Inhibiting MMP activity prevents the development of endometriosis in the chicken chorioallantoic membrane model[J]. Hum Reprod, 2004, 19(10): 2180-2187.
13.	Hofmann UB, Westphal JR, Van Kraats AA, et al. Expression of integrin alpha(v)beta(3) correlates with activation of membrane-type matrix metalloproteinase-1 (MT1-MMP) and matrix metalloproteinase-2 (MMP-2) in human melanoma cells in vitro and in vivo[J]. Int J Cancer, 2000, 87(1): 12-19.
14.	Sillem M, Prifti S, Koch A, et al. Regulation of matrix metalloproteinases and their inhibitors in uterine endometrial cells of patients with and without endometriosis[J]. Eur J Obstet Gynecol Reprod Biol, 2001, 95(2): 167-174.
15.	蔡蕾, 袁卿, 龙雯晴, 等. 米非司酮治疗后MMP-9和TIMP-1在异位和在位子宫内膜中的表达[J]. 上海交通大学学报·医学版, 2007, 27(8): 981-983.
16.	Papp C, Schatz F, Krikun G, et al. Biological mechanisms underlying the clinical effects of mifepristone (RU 486) on the endometrium[J]. Early Pregnancy, 2000, 4(4): 230-239.
17.	Newfield RS, Spitz IM, Isacson C, et al. Long-term mifepristone (RU486) therapy resulting in massive benign endometrial hyperplasia[J]. Clin Endocrinol (Oxf), 2001, 54(3): 399-404.

1. 　郎景和. 子宫内膜异位症研究的任务与展望(之一)[J]. 中华妇产科杂志, 2006, 41(5): 289-290.
2. 　Kettel LM, Murphy AA, Mortola JF, et al. Endocrine responses to long-term administration of the antiprogesterone RU486 in patients with pelvic endometriosis[J]. Fertil Steril, 1991, 56(3): 402-407.
3. 　张曦, 王鑫, 王红静, 等. 大鼠子宫内膜异位症模型建立方法的探索[J]. 华西医学, 2007, 22(4): 831-833.
4. 　刘万里, 薛茜, 曹明芹, 等. 用SPSS实现完全随机设计多组比较秩和检验的多重比较[J]. 地方病通报, 2007, 22(2): 27-29.
5. 　Melin A, Sparén P, Persson I, et al. Endometriosis and the risk of Cancer with special emphasis on ovarian Cancer[J]. Hum Reprod, 2006, 21(5): 1237-1242.
6. 　邬巧霞. 腹腔镜手术联合米非司酮治疗子宫内膜异位症的临床研究[J]. 中国妇幼保健, 2010, 25(23): 3355-3356.
7. 　周夏伶, 许剑利, 乔林, 等. 米非司酮治疗子宫内膜异位症临床效果观察[J]. 中国计划生育学杂志, 2009, 159(1): 36-38.
8. 　Sidell N, Han SW, Parthasarathy S. Regulation and modulation of abnormal immune responses in endometriosis[J]. Ann N Y Acad Sci, 2002, 955: 159-173.
9. 　Li X, Bao Y, Fang P, et al. Effect of mifepristone on COX-2 both in eutopic and ectopic endometrium in mouse endometriotic model[J]. Arch Gynecol Obstet, 2012, 286(4): 939-946.
10. 　Di Carlo A. Matrix metalloproteinase-2 and -9 in the sera and in the urine of human oncocytoma and renal cell carcinoma[J]. Oncol Rep, 2012, 28(3): 1051-1056.
11. 　Reis ST, Leite KR, Piovesan LF, et al. Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer[J]. BMC Urol, 2012, 12: 18.
12. 　Nap AW, Dunselman GA, de Goeij AF, et al. Inhibiting MMP activity prevents the development of endometriosis in the chicken chorioallantoic membrane model[J]. Hum Reprod, 2004, 19(10): 2180-2187.
13. 　Hofmann UB, Westphal JR, Van Kraats AA, et al. Expression of integrin alpha(v)beta(3) correlates with activation of membrane-type matrix metalloproteinase-1 (MT1-MMP) and matrix metalloproteinase-2 (MMP-2) in human melanoma cells in vitro and in vivo[J]. Int J Cancer, 2000, 87(1): 12-19.
14. 　Sillem M, Prifti S, Koch A, et al. Regulation of matrix metalloproteinases and their inhibitors in uterine endometrial cells of patients with and without endometriosis[J]. Eur J Obstet Gynecol Reprod Biol, 2001, 95(2): 167-174.
15. 　蔡蕾, 袁卿, 龙雯晴, 等. 米非司酮治疗后MMP-9和TIMP-1在异位和在位子宫内膜中的表达[J]. 上海交通大学学报·医学版, 2007, 27(8): 981-983.
16. 　Papp C, Schatz F, Krikun G, et al. Biological mechanisms underlying the clinical effects of mifepristone (RU 486) on the endometrium[J]. Early Pregnancy, 2000, 4(4): 230-239.
17. 　Newfield RS, Spitz IM, Isacson C, et al. Long-term mifepristone (RU486) therapy resulting in massive benign endometrial hyperplasia[J]. Clin Endocrinol (Oxf), 2001, 54(3): 399-404.

West China Medical Journal

Effect of Different Therapeutic Regimens of Mifepristone on the Expression of Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Endometriotic Rats

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