• 1 核工業(yè)416醫(yī)院泌尿外科（成都，610051）;2 邛崍市醫(yī)療中心醫(yī)院男科;3 成都中醫(yī)藥大學(xué)附屬醫(yī)院男科;

【摘要】　目的　 評(píng)價(jià)非那雄胺對(duì)良性前列腺增生（benign prostate hyperplasia，BPH）細(xì)胞外基質(zhì)（extracellular matrixc，ECM）的影響，并探討其作用機(jī)制。　方法　 2008年6月－2009年3月選擇具備手術(shù)指征的BPH患者20例，按入院順序隨機(jī)分為非那雄胺組和安慰劑組。服藥4周后，行經(jīng)尿道前列腺切除術(shù)（transurethral resection prostate，TURP），留取組織標(biāo)本。另取正常前列腺標(biāo)本6例，用免疫組織化學(xué)法結(jié)合圖像分析系統(tǒng)研究正常組、安慰劑組和非那雄胺組前列腺組織纖維連接蛋白（FN）、膠原（CL）、基質(zhì)金屬蛋白酶2（MMP-2）、金屬蛋白酶組織抑制因子2（TIMP-2）的陽(yáng)性表達(dá)。　結(jié)果　 安慰劑組前列腺組織的FN、CL的陽(yáng)性表達(dá)較正常組增強(qiáng)（P lt;0.01），MMP-2/TIMP-2差異無(wú)統(tǒng)計(jì)學(xué)意義（P gt;0.05）；非那雄胺組與安慰劑組相比，F(xiàn)N、CL的陽(yáng)性表達(dá)減弱（P lt;0.01），而MMP-2/TIMP-2增高（P lt;0.01）。　結(jié)論　 非那雄胺能降低BPH組織ECM成分，避免其沉積，其作用機(jī)制可能與其促進(jìn)ECM降解有關(guān)。
【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.

引用本文： 邵繼春,聶明,王林,張蜀武. 非那雄胺對(duì)增生前列腺組織細(xì)胞外基質(zhì)的影響. 華西醫(yī)學(xué), 2011, 26(7): 1054-1058. doi: 復(fù)制

1. 　欒蓉, 劉穎, 趙春杰, 等. 非那雄胺片人體藥代動(dòng)力學(xué)及生物等效性研究[J]. 藥物研究, 2011, 20(1): 15-16.
2. 　高歌, 艾自勝. 使用計(jì)算機(jī)隨機(jī)分組與隨機(jī)抽樣的方法及應(yīng)用[J]. 中國(guó)衛(wèi)生統(tǒng)計(jì), 2002, 19(1): 48-49.
3. 　李玉林. 分子病理學(xué)[M]. 北京: 人民衛(wèi)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. 細(xì)胞外基質(zhì)的結(jié)構(gòu)與功能(續(xù))[J]. 西南國(guó)防醫(yī)藥, 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, 方玉華. 人良性前列腺增生組織中性激素結(jié)合位點(diǎn)與細(xì)胞外基質(zhì)的研究[J]. 中華泌尿外科雜志, 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, 侯淑蘭, 等. 良性前列腺增生組織中細(xì)胞外基質(zhì)與生長(zhǎng)轉(zhuǎn)化因子-β的研究[J]. 中華泌尿外科志, 1995, 16(7): 421-422.
10. 　李月明, 李玉魁, 杜群先. 大鼠良性前列腺增生組織中細(xì)胞外基質(zhì)的免疫組化研究[J]. 北京軍區(qū)醫(yī)藥, 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. 　鄧方明, 夏同禮, 顧方六. 前列腺發(fā)育、增生和癌的間質(zhì)-上皮相互作用機(jī)制[J]. 中華泌尿外科雜志, 1994, 15(2): 139-142.
15. 　牛遠(yuǎn)杰, 董克權(quán), 馬騰驤. 良性前列腺增生癥的間質(zhì)-上皮相互作用機(jī)制[J]. 中華泌尿外科雜志, 1996, 17(6): 379-382.
16. 　余帆. 宋波. 熊恩慶. 雄激素、間質(zhì)、上皮在前列腺增生中的相互作用[J]. 國(guó)外醫(yī)學(xué)?泌尿系統(tǒng)分冊(cè), 1998, 18(2): 60-62.
17. 　崔京, 黃健, 方銀杏. 非那雄胺的藥理和臨床應(yīng)用[J]. 國(guó)外醫(yī)學(xué)?合成藥、生化藥、制劑分冊(cè), 2002, 23(1): 35-37.
18. 　楊小麗, 宣強(qiáng), 黃逢雨, 等. 前列腺增生間質(zhì)對(duì)上皮細(xì)胞組織激肽釋放酶7表達(dá)的影響[J]. 中華男科學(xué)雜志, 2011, 17(4): 305-309.
19. 　李艷, 陳楠. 細(xì)胞外基質(zhì)的降解與MMPs/TIMPs[J]. 上海醫(yī)學(xué), 2000, 23(11): 701-704.
20. 　許志強(qiáng), 劉平. 細(xì)胞外基質(zhì)的結(jié)構(gòu)與功能[J]. 中國(guó)肝病學(xué)雜志, 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. 1. 　欒蓉, 劉穎, 趙春杰, 等. 非那雄胺片人體藥代動(dòng)力學(xué)及生物等效性研究[J]. 藥物研究, 2011, 20(1): 15-16.
  2. 2. 　高歌, 艾自勝. 使用計(jì)算機(jī)隨機(jī)分組與隨機(jī)抽樣的方法及應(yīng)用[J]. 中國(guó)衛(wèi)生統(tǒng)計(jì), 2002, 19(1): 48-49.
  3. 3. 　李玉林. 分子病理學(xué)[M]. 北京: 人民衛(wèi)生出版社, 2002: 251-260.
  4. 4. 　Raghow R. The role of extracellular matrix in postinflammatory wound healing and fibrosis[J]. FASEB J, 1994, 8(11): 823-831.
  5. 5. 　舒崇湘, 程天民. 細(xì)胞外基質(zhì)的結(jié)構(gòu)與功能(續(xù))[J]. 西南國(guó)防醫(yī)藥, 2001, 11(3): 220-223.
  6. 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. 7. 　李月明, 方玉華. 人良性前列腺增生組織中性激素結(jié)合位點(diǎn)與細(xì)胞外基質(zhì)的研究[J]. 中華泌尿外科雜志, 1994, 15(4): 269-271.
  8. 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. 9. 　李月明, 李玉魁, 侯淑蘭, 等. 良性前列腺增生組織中細(xì)胞外基質(zhì)與生長(zhǎng)轉(zhuǎn)化因子-β的研究[J]. 中華泌尿外科志, 1995, 16(7): 421-422.
  10. 10. 　李月明, 李玉魁, 杜群先. 大鼠良性前列腺增生組織中細(xì)胞外基質(zhì)的免疫組化研究[J]. 北京軍區(qū)醫(yī)藥, 1996, 8(6): 407-409.
  11. 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. 12. 　Roberts AB, Mc Cune BK, Sporn MB. TGF-β: Regulation of extracellular matrix[J]. Kidney International. 1992, 41(3): 577-559.
  13. 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. 14. 　鄧方明, 夏同禮, 顧方六. 前列腺發(fā)育、增生和癌的間質(zhì)-上皮相互作用機(jī)制[J]. 中華泌尿外科雜志, 1994, 15(2): 139-142.
  15. 15. 　牛遠(yuǎn)杰, 董克權(quán), 馬騰驤. 良性前列腺增生癥的間質(zhì)-上皮相互作用機(jī)制[J]. 中華泌尿外科雜志, 1996, 17(6): 379-382.
  16. 16. 　余帆. 宋波. 熊恩慶. 雄激素、間質(zhì)、上皮在前列腺增生中的相互作用[J]. 國(guó)外醫(yī)學(xué)?泌尿系統(tǒng)分冊(cè), 1998, 18(2): 60-62.
  17. 17. 　崔京, 黃健, 方銀杏. 非那雄胺的藥理和臨床應(yīng)用[J]. 國(guó)外醫(yī)學(xué)?合成藥、生化藥、制劑分冊(cè), 2002, 23(1): 35-37.
  18. 18. 　楊小麗, 宣強(qiáng), 黃逢雨, 等. 前列腺增生間質(zhì)對(duì)上皮細(xì)胞組織激肽釋放酶7表達(dá)的影響[J]. 中華男科學(xué)雜志, 2011, 17(4): 305-309.
  19. 19. 　李艷, 陳楠. 細(xì)胞外基質(zhì)的降解與MMPs/TIMPs[J]. 上海醫(yī)學(xué), 2000, 23(11): 701-704.
  20. 20. 　許志強(qiáng), 劉平. 細(xì)胞外基質(zhì)的結(jié)構(gòu)與功能[J]. 中國(guó)肝病學(xué)雜志, 1999, 4(2): 92-93.
  21. 21. 　Back M, Ketelhuth DF, Agewall S. Matrix metalloproteinasein atherothrombosis[J]. Prog Cardiovasc Dis, 2010, 52(5): 410-428.