通关胶囊对TURP术中出血和前列腺组织血管形成影响的机理研究
摘要
目的：评价通关胶囊对良性前列腺增生(BPH)患者行经尿道前列腺电切术(TURP)术中出血的影响，并从血管形成的角度探讨通关胶囊减少TURP术中出血的机理。
方法：选择具备手术指征的BPH病人39例，应用1∶1∶1随机数字表，按入院顺序随机分为通关胶囊组、非那雄胺组和安慰剂组。服药2周后，行TURP术，计算术中出血量、切除每克腺体出血量和每分钟出血量。用免疫组化法结合图像分析系统研究正常组、安慰剂组、非那雄胺组和通关胶囊组前列腺组织AC133、KDR、HIF-1的阳性表达。
结果：通关胶囊组和非那雄胺组的术中出血总量、每克腺体出血量、每分钟出血量与安慰剂组相比均明显减少(P＜0.05)；免疫组化结合图象分析系统研究结果表明，安慰剂组前列腺组织的AC133、KDR、HIF-1的阳性表达较正常组显著增强(P＜0.01)；通关胶囊组、非那雄胺组前列腺组织的上述指标的阳性表达则较安慰剂组明显减弱(P＜0.05或P＜0.01)。
结论：BPH与血管形成有关。通关胶囊能减少TURP术中出血，其机理可能与抑制增生前列腺组织AC133、KDR、HIF-1的表达，进而抑制BPH血管形成有关。
Objective: To evaluate influence of Tongguan Capsule on bleeding during TURP on BPH patients and study mechanism of it inhibiting bleeding during TURP through the point of vasculogenesis on BPH.
Methods: 39 BPH patients, having surgery sign, were randomly divided into 3 groups-Tongguan Capsule group, finasteride group and placebo group with each group having 13 patients according to hospitalizing orders. TURP were operated and general bleeding volume, bleeding volume per gram and bleeding volume per minute were calculated after 2 weeks of administration. Expressions of AC 133 antigen, KDR and HIF-1 were studied in prostatic tissues in all groups (including normal group) by immunohistochemistry and image analysis system.
Results: General bleeding volume, bleeding volume per gram and bleeding volume per minute in both Tongguan Capsule group and finasteride group decreased significantly compared with those of placebo group (P<0.05). The results of immunohistochemistry and image analysis system manifested that expressions of AC 133 antigen, KDR and HIF-1 in hyperplastic prostate of placebo group significantly increased compared with those of normal group,at the same time,those of both Tongguan Capsule group and finateride group significantly reduced compared with those of placebo group(P<0.05 or P<0.01).
Conclusions: BPH is related to vasculogenesis. Tongguan Capsule can reduce bleeding during TURP. The principle is possible related to inhibiting Expressions of AC 133 antigen, KDR and HIF-1 in BPH and then inhibiting vasculogenesis.
方法：选择具备手术指征的BPH病人39例，应用1∶1∶1随机数字表，按入院顺序随机分为通关胶囊组、非那雄胺组和安慰剂组。服药2周后，行TURP术，计算术中出血量、切除每克腺体出血量和每分钟出血量。用免疫组化法结合图像分析系统研究正常组、安慰剂组、非那雄胺组和通关胶囊组前列腺组织AC133、KDR、HIF-1的阳性表达。
结果：通关胶囊组和非那雄胺组的术中出血总量、每克腺体出血量、每分钟出血量与安慰剂组相比均明显减少(P＜0.05)；免疫组化结合图象分析系统研究结果表明，安慰剂组前列腺组织的AC133、KDR、HIF-1的阳性表达较正常组显著增强(P＜0.01)；通关胶囊组、非那雄胺组前列腺组织的上述指标的阳性表达则较安慰剂组明显减弱(P＜0.05或P＜0.01)。
结论：BPH与血管形成有关。通关胶囊能减少TURP术中出血，其机理可能与抑制增生前列腺组织AC133、KDR、HIF-1的表达，进而抑制BPH血管形成有关。
Objective: To evaluate influence of Tongguan Capsule on bleeding during TURP on BPH patients and study mechanism of it inhibiting bleeding during TURP through the point of vasculogenesis on BPH.
Methods: 39 BPH patients, having surgery sign, were randomly divided into 3 groups-Tongguan Capsule group, finasteride group and placebo group with each group having 13 patients according to hospitalizing orders. TURP were operated and general bleeding volume, bleeding volume per gram and bleeding volume per minute were calculated after 2 weeks of administration. Expressions of AC 133 antigen, KDR and HIF-1 were studied in prostatic tissues in all groups (including normal group) by immunohistochemistry and image analysis system.
Results: General bleeding volume, bleeding volume per gram and bleeding volume per minute in both Tongguan Capsule group and finasteride group decreased significantly compared with those of placebo group (P<0.05). The results of immunohistochemistry and image analysis system manifested that expressions of AC 133 antigen, KDR and HIF-1 in hyperplastic prostate of placebo group significantly increased compared with those of normal group,at the same time,those of both Tongguan Capsule group and finateride group significantly reduced compared with those of placebo group(P<0.05 or P<0.01).
Conclusions: BPH is related to vasculogenesis. Tongguan Capsule can reduce bleeding during TURP. The principle is possible related to inhibiting Expressions of AC 133 antigen, KDR and HIF-1 in BPH and then inhibiting vasculogenesis.
引文
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5. Tepper OM, Geliano RD, Kalka C. et al. Endothelial progenitor cell:the promise of vascular stem cells for plastic surgery[J].Plast reconstr Surg. 2003, 111(2): 846～854
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2．张蜀武，常德贵，邵继春等．通关胶囊治疗前列腺增生的临床研究及机理探讨．中国中西医结合外科杂志，2001：7(1)：10～13
3．张蜀武，常德贵，王久源，等．通关胶囊对人离体增生前列腺组织α_1-受体的拮抗作用．中华思科学，2001；7(2)：7～10
4．张蜀武，邵继春，常德贵．通关胶囊抑制大鼠前列腺组织细胞增殖的机理．现代泌尿外科学，2002：3
5. Tepper OM, Geliano RD, Kalka C. et al. Endothelial progenitor cell:the promise of vascular stem cells for plastic surgery[J].Plast reconstr Surg. 2003, 111(2): 846～854
6．王伯云，李玉松，黄高升主编．病理学技术．人民卫生出版社，2000年6月第1版，354～437
7．许良中主编．实用肿瘤病理方法学．上海医科大学出版社，1997年9月第1版，161～175
8．王毅，郑燕林，仝崇毅．水蛭素对外伤性增生性玻璃体视网膜病变增殖膜抑制机制的探讨．中国中医眼科杂志，2002，(4)：187～191
9．成令忠．组织学．北京：人民卫生出版社，1994：30～31
10．刘国廉．细胞毒理学．北京：军事医学科学出版社．200l：130～143
11．申洪，沈忠英．实用生物体视学技术．广州：中山大学出版社，1991：8(1)：64～152
12．王毅，邵继春，张蜀武．雄激素致去势大鼠前列腺增生的组织形态学研究．中华男科学，2002，(3)：190～193
13．李玉林，叶诸榕，龚守良．分子病理学，人民卫生出版社。2002：175～176
14. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis [J]Scienece, 1997, 275 (5302):964～967
15. Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial prognitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization [J]. Circ Pes, 1999, g5(3):221～228
16. Choi K, Kennedy M Kazarov A et al. A common precusor for hematopoietic and endothelial cell [J]. Development, 1998, 125(4): 725～732
17. Kalka C, Masuda H, Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cell for therapeutic neovascularization [J]. Proc Natl Acad Sci USA, 2000, 97(7) :3422～3427
18. Murohara T, Ikeda H,Duan JL, et al. Transplantated cord blood-derived endothelial procursor cells augment postnatal neovascularization [J]. J Clin Invest. 2000, 105(11):1527～1536
19. Folkman J. Is tissue mass regulated by vascular endothelial cell prostate as the first evidence. Endocrinology, 1998, 139:441～442
20．顾方六．现代前列腺病学．北京：人民军医出版社，2002：77
21. Hristov M, Erl W, Weber PC. Endothelial progenitor cell culture and differentiation in vito: a methodological comparison using human umbilical cord blood[J].Cardiovasic Res, 2003, 58(2):478～486
22．金有豫．药理学，人民卫生出版社．2001：10～12
23. Mc Connell JD, Bruskewitz R, Walsh P, et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among
men with benign prostate hyperplasia[J]. N Engl J Med, 1998; 338(9):557～563
24. Sieber PR, Ronmel FM, Huffnagle HW, et al. The treatment of gross hematuria secondary to prostatic bleeding with finasteride[J].J Urol, 1998, 159(4):1232～1233
25．刘树硕，史时芳，谢家俊．非那雄胺对小鼠前列腺组织血管内皮细胞生长因子表达的影响．现代泌尿外科杂志，2002，7(2)：92～94
26．刘孝东，杨宇如，卢一平等．非那雄胺减少TURP术中出血的机理研究．中华泌尿外科杂志，2003，10(24)：694～696
27．韩冰，郑继成，杨文增．良性前列腺增生患者的血液流变观察．临床泌尿外科杂志，1993，8(2)：104
28. Miraglia S, Godfrey W, YIN AH, et al. A novel five-transmembrane hematopoietic stem cell antigen:isolation, characterizantion,and molecular cloning. Blood,1997, 90:5013～5021
29. Pasino M, Lanza T, Marotta F, et al. Flow cytometric and functional charaterization of AC133~+cells from human umbilical cord blood Br J Haematol, 2000, 108:793～800
30. De Wynter EA, Buck D, Hart C. et al. CD34~+AC133~+cells isolated from cord blood are highly enriched in long-term culture-initiating cells,NOD/SCID-repopulating cells and dendritic cell progenitors. Stem Cells,1998, 16:387～396
31. Gousseti E, Theodosake M, Paterakes G, et al. A functional hierarchy among the CD34+ hematopoietic cells based on in vitro proliferative and differentiative potential of AC133+ CD34b(right) and AC133(dim/)-CD34+ human cord blood cells. J Hematother Stem Cell Res, 2000, 9:827～840
32. Matsumoto K, Yasui K, Yamashita N, et al. In vitro proliferation potential of AC133 positive cells in peripheral blood. Stem Cells, 2000, 18:196～203
33. Gehling UM, Ergun S, Schumacher U, et al. [J]. Blood, 2000, 95(i0): 3106～3112
34. Reyes M, Dudek A, Jahagerdar B, et al. [J] J Clin Invest, 2002, 109(3):337～346
35. Quirici N, Soligo D, Caneva L, et al. Differentiation and expansion of endothelial cells from human bone marrow CD133(+) cells. Br J Haematol.2001 Oct; 115(I):186～94
36．钱朝南，闵华庆．血管内皮生长因子的研究进展[J]．中国病理生理杂志，1999，15(8)：855～859
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