Influence of Finasteride on Extracellular Matrix in Benign Prostate Hyperplasia Patients and Its Mechanism_West China Medical Journal

Authors：

SHAO Jichun ¹ , NIE Ming ¹ , WANG Lin ² , ZHANG Shuwu ³

1. Department of Urology, Chengdu 416 Hospital, Chengdu, Sichuan 610051, P. R. China; 2. Department of Andrology, Qionglai Medical Center Hospital, Qionglai, Sichuan 611530, P. R. China; 3. Department of Andrology, Affiliated Hospital of Chengdu University of TCM, Chengdu, Sichuan 610072, P. R. China;

Corresponding author：

Keywords：

非那雄胺; 前列腺增生; 细胞外基质

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【摘要】　目的　评价非那雄胺对良性前列腺增生（benign prostate hyperplasia，BPH）细胞外基质（extracellular matrixc，ECM）的影响，并探讨其作用机制。　方法　 2008年6月－2009年3月选择具备手术指征的BPH患者20例，按入院顺序随机分为非那雄胺组和安慰剂组。服药4周后，行经尿道前列腺切除术（transurethral resection prostate，TURP），留取组织标本。另取正常前列腺标本6例，用免疫组织化学法结合图像分析系统研究正常组、安慰剂组和非那雄胺组前列腺组织纤维连接蛋白（FN）、胶原（CL）、基质金属蛋白酶2（MMP-2）、金属蛋白酶组织抑制因子2（TIMP-2）的阳性表达。　结果　安慰剂组前列腺组织的FN、CL的阳性表达较正常组增强（P lt;0.01），MMP-2/TIMP-2差异无统计学意义（P gt;0.05）；非那雄胺组与安慰剂组相比，FN、CL的阳性表达减弱（P lt;0.01），而MMP-2/TIMP-2增高（P lt;0.01）。　结论　非那雄胺能降低BPH组织ECM成分，避免其沉积，其作用机制可能与其促进ECM降解有关。
【Abstract】　Objective　 To evaluate influence of finasteride on extracellular matrix (ECM) in benign prostate hyperplasia (BPH) patients and study the mechanism.　Methods　 Twenty BPH patients needing surgery were randomly divided into 2 groups according to the sequence of hospitalization from June 2008 to March 2009. The finasteride group and the placebo group had 10 patients each. Transurethral resection prostate (TURP) were performed and the specimens were collected after 4 weeks of drug administration. Moreover, 6 normal prostatic tissues were selected. Expressions of fibronectin (FN), collagen (CL), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) were studied in prostatic tissues in all groups (including the normal group) by immunohistochemistry and image analysis system.　Results　 Expressions of FN and CL were significantly higher than those in the normal group (P lt;0.01), while expressions of MMP-2 and TIMP-2 were not significantly different between them (P gt;0.05). Compared with the placebo group, expressions of FN and CL in the finateride group were significantly lower than the placebo group (P lt;0.01), while expressions of MMP-2 and TIMP-2 were significantly higher (P lt;0.01).　Conclusions　 BPH is related to ECM depositing. Finasteride can decrease ECM of BPH and refrain it from depositing. Possibly, the principle is that finasteride can promote the degradation of ECM.

Citation： SHAO Jichun,NIE Ming,WANG Lin,ZHANG Shuwu. Influence of Finasteride on Extracellular Matrix in Benign Prostate Hyperplasia Patients and Its Mechanism. West China Medical Journal, 2011, 26(7): 1054-1058. doi: Copy

1.	栾蓉, 刘颖, 赵春杰, 等. 非那雄胺片人体药代动力学及生物等效性研究[J]. 药物研究, 2011, 20(1): 15-16.
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8.	Von Der Mark K, Von Der Mark H. Goodman S. Celluar respones to extracellular matrix[J]. Kidney Internationa1, 1992, 41(2): 632-640.
9.	李月明, 李玉魁, 侯淑兰, 等. 良性前列腺增生组织中细胞外基质与生长转化因子-β的研究[J]. 中华泌尿外科志, 1995, 16(7): 421-422.
10.	李月明, 李玉魁, 杜群先. 大鼠良性前列腺增生组织中细胞外基质的免疫组化研究[J]. 北京军区医药, 1996, 8(6): 407-409.
11.	Lubrano C, Petrangcli E. Catisonc A, et al. Epidermal growth factor binding and steroid receptor content in human benign prostatic hyperplasia[J]. Steroid Biochem, 1989, 34(1-6): 499-504.
12.	Roberts AB, Mc Cune BK, Sporn MB. TGF-β: Regulation of extracellular matrix[J]. Kidney International. 1992, 41(3): 577-559.
13.	Freeman MR, Song Y, Garson PD, et al. Extracellular matrix and androgen receptor expression associated with spontaneous transformation of rat prostate fibroblast[J]. Cancer Res, 1991, 51(7): 1910-1916.
14.	邓方明, 夏同礼, 顾方六. 前列腺发育、增生和癌的间质-上皮相互作用机制[J]. 中华泌尿外科杂志, 1994, 15(2): 139-142.
15.	牛远杰, 董克权, 马腾骧. 良性前列腺增生症的间质-上皮相互作用机制[J]. 中华泌尿外科杂志, 1996, 17(6): 379-382.
16.	余帆. 宋波. 熊恩庆. 雄激素、间质、上皮在前列腺增生中的相互作用[J]. 国外医学•泌尿系统分册, 1998, 18(2): 60-62.
17.	崔京, 黄健, 方银杏. 非那雄胺的药理和临床应用[J]. 国外医学•合成药、生化药、制剂分册, 2002, 23(1): 35-37.
18.	杨小丽, 宣强, 黄逢雨, 等. 前列腺增生间质对上皮细胞组织激肽释放酶7表达的影响[J]. 中华男科学杂志, 2011, 17(4): 305-309.
19.	李艳, 陈楠. 细胞外基质的降解与MMPs/TIMPs[J]. 上海医学, 2000, 23(11): 701-704.
20.	许志强, 刘平. 细胞外基质的结构与功能[J]. 中国肝病学杂志, 1999, 4(2): 92-93.
21.	Back M, Ketelhuth DF, Agewall S. Matrix metalloproteinasein atherothrombosis[J]. Prog Cardiovasc Dis, 2010, 52(5): 410-428.

1. 　栾蓉, 刘颖, 赵春杰, 等. 非那雄胺片人体药代动力学及生物等效性研究[J]. 药物研究, 2011, 20(1): 15-16.
2. 　高歌, 艾自胜. 使用计算机随机分组与随机抽样的方法及应用[J]. 中国卫生统计, 2002, 19(1): 48-49.
3. 　李玉林. 分子病理学[M]. 北京: 人民卫生出版社, 2002: 251-260.
4. 　Raghow R. The role of extracellular matrix in postinflammatory wound healing and fibrosis[J]. FASEB J, 1994, 8(11): 823-831.
5. 　舒崇湘, 程天民. 细胞外基质的结构与功能(续)[J]. 西南国防医药, 2001, 11(3): 220-223.
6. 　Kimball FA, Buhl AE, Carter DB. New approaches to the study of benign prostatic hyperplasia[M]. New York: Alan R. Liss, 1984: 179.
7. 　李月明, 方玉华. 人良性前列腺增生组织中性激素结合位点与细胞外基质的研究[J]. 中华泌尿外科杂志, 1994, 15(4): 269-271.
8. 　Von Der Mark K, Von Der Mark H. Goodman S. Celluar respones to extracellular matrix[J]. Kidney Internationa1, 1992, 41(2): 632-640.
9. 　李月明, 李玉魁, 侯淑兰, 等. 良性前列腺增生组织中细胞外基质与生长转化因子-β的研究[J]. 中华泌尿外科志, 1995, 16(7): 421-422.
10. 　李月明, 李玉魁, 杜群先. 大鼠良性前列腺增生组织中细胞外基质的免疫组化研究[J]. 北京军区医药, 1996, 8(6): 407-409.
11. 　Lubrano C, Petrangcli E. Catisonc A, et al. Epidermal growth factor binding and steroid receptor content in human benign prostatic hyperplasia[J]. Steroid Biochem, 1989, 34(1-6): 499-504.
12. 　Roberts AB, Mc Cune BK, Sporn MB. TGF-β: Regulation of extracellular matrix[J]. Kidney International. 1992, 41(3): 577-559.
13. 　Freeman MR, Song Y, Garson PD, et al. Extracellular matrix and androgen receptor expression associated with spontaneous transformation of rat prostate fibroblast[J]. Cancer Res, 1991, 51(7): 1910-1916.
14. 　邓方明, 夏同礼, 顾方六. 前列腺发育、增生和癌的间质-上皮相互作用机制[J]. 中华泌尿外科杂志, 1994, 15(2): 139-142.
15. 　牛远杰, 董克权, 马腾骧. 良性前列腺增生症的间质-上皮相互作用机制[J]. 中华泌尿外科杂志, 1996, 17(6): 379-382.
16. 　余帆. 宋波. 熊恩庆. 雄激素、间质、上皮在前列腺增生中的相互作用[J]. 国外医学•泌尿系统分册, 1998, 18(2): 60-62.
17. 　崔京, 黄健, 方银杏. 非那雄胺的药理和临床应用[J]. 国外医学•合成药、生化药、制剂分册, 2002, 23(1): 35-37.
18. 　杨小丽, 宣强, 黄逢雨, 等. 前列腺增生间质对上皮细胞组织激肽释放酶7表达的影响[J]. 中华男科学杂志, 2011, 17(4): 305-309.
19. 　李艳, 陈楠. 细胞外基质的降解与MMPs/TIMPs[J]. 上海医学, 2000, 23(11): 701-704.
20. 　许志强, 刘平. 细胞外基质的结构与功能[J]. 中国肝病学杂志, 1999, 4(2): 92-93.
21. 　Back M, Ketelhuth DF, Agewall S. Matrix metalloproteinasein atherothrombosis[J]. Prog Cardiovasc Dis, 2010, 52(5): 410-428.

West China Medical Journal

Influence of Finasteride on Extracellular Matrix in Benign Prostate Hyperplasia Patients and Its Mechanism

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