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; 子宮內膜異位癥; 大鼠; 基質金屬蛋白酶-9; 基質金屬蛋白酶組織特異性抑制物-1

DOI：

10.7507/1002-0179.20130275

Video：

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目的　探討不同劑量和不同療程米非司酮對大鼠子宮異位內膜基質金屬蛋白酶-9（MMP-9）及其組織特異性抑制物-1（TIMP-1）表達的影響。方法　65只子宮內膜異位癥大鼠隨機分為低劑量組、高劑量組、對照組。各個劑量組分別灌胃20、30、40 d后取異位子宮內膜組織用免疫組織化學法檢測MMP-9及TIMP-1的表達，并計算MMP-9/TIMP-1比值。結果　低劑量組和高劑量組均能使異位內膜MMP-9表達下降（P＜0.05）,TIMP-1表達升高（P＜0.05）,高劑量組的作用更加明顯，與低劑量組差異有統計學意義（P＜0.05）；用藥30 d低劑量組TIMP-1表達最高，與用藥20 d和40 d相比差異有統計學意義（P＜0.05）,同樣高劑量組用藥30d TIMP-1的表達也最高，與用藥20 d和用藥40 d比較差異有統計學意義（P＜0.05）。與用藥20、40 d比較差異有統計學意義（P＜0.05）。結論　米非司酮能夠降低大鼠異位子宮內膜的侵襲能力，高劑量米非司酮抑制效果更明顯；用藥30 d米非司酮對大鼠異位內膜的侵襲能力抑制最強，延長用藥時間不能使異位內膜侵襲能力繼續下降。

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. 子宮內膜異位癥研究的任務與展望(之一)[J]. 中華婦產科雜志, 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.	張曦, 王鑫, 王紅靜, 等. 大鼠子宮內膜異位癥模型建立方法的探索[J]. 華西醫學, 2007, 22(4): 831-833.
4.	劉萬里, 薛茜, 曹明芹, 等. 用SPSS實現完全隨機設計多組比較秩和檢驗的多重比較[J]. 地方病通報, 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.	鄔巧霞. 腹腔鏡手術聯合米非司酮治療子宮內膜異位癥的臨床研究[J]. 中國婦幼保健, 2010, 25(23): 3355-3356.
7.	周夏伶, 許劍利, 喬林, 等. 米非司酮治療子宮內膜異位癥臨床效果觀察[J]. 中國計劃生育學雜志, 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, 龍雯晴, 等. 米非司酮治療后MMP-9和TIMP-1在異位和在位子宮內膜中的表達[J]. 上海交通大學學報·醫學版, 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. 子宮內膜異位癥研究的任務與展望(之一)[J]. 中華婦產科雜志, 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. 　張曦, 王鑫, 王紅靜, 等. 大鼠子宮內膜異位癥模型建立方法的探索[J]. 華西醫學, 2007, 22(4): 831-833.
4. 　劉萬里, 薛茜, 曹明芹, 等. 用SPSS實現完全隨機設計多組比較秩和檢驗的多重比較[J]. 地方病通報, 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. 　鄔巧霞. 腹腔鏡手術聯合米非司酮治療子宮內膜異位癥的臨床研究[J]. 中國婦幼保健, 2010, 25(23): 3355-3356.
7. 　周夏伶, 許劍利, 喬林, 等. 米非司酮治療子宮內膜異位癥臨床效果觀察[J]. 中國計劃生育學雜志, 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, 龍雯晴, 等. 米非司酮治療后MMP-9和TIMP-1在異位和在位子宮內膜中的表達[J]. 上海交通大學學報·醫學版, 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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