睾酮刺激大鼠前列腺增生模型的血管新生及调控因子研究  

Angiogenesis and Regulatory Factors in Rats with BPH Induced by Testosterone

作　　者：邵继春[1] 王毅[2] 张蜀武[1] 罗德康[1] 常德贵[1] 吴先奇[1] 唐民[1] 何梓铭[3] 

机构地区：[1]成都中医药大学附属医院泌尿外科,四川成都610072 [2]成都中医药大学附属医院病理科,四川成都610072 [3]重庆医科大学附属第一医院泌尿外科,重庆400016

出　　处：《中华男科学杂志》2005年第6期413-418,共6页National Journal of Andrology

基　　金：四川省教育厅重点项目资助(01LA53)

摘　　要：目的:探讨血管新生(angiogenesis)及调控因子与睾酮刺激大鼠良性前列腺增生(BPH)的关系.方法:16只8周龄200～250 g SD大鼠随机分为对照组与模型组各8只,采用去势后皮下注射丙酸睾酮法建立大鼠BPH模型.应用免疫组化结合图像分析系统检测对照组、BPH模型组前列腺组织微血管密度(MVD)、血管内皮生长因子(VEGF)、血管内皮生长因子受体1(flk-1)、内皮抑素(endostatin)、基质金属蛋白酶2(MMP-2)及其抑制剂(TIMP-2)的表达,并使用逐步引入剔除模型进行多元回归分析.结果:BPH模型组前列腺组织MVD明显增高(P＜0.01),VEGF、flk-1、MMP-2的表达及MMP-2/TIMP-2、VEGF/endostatin比值均高于对照组(P＜0.01),endostatin阳性表达低于对照组(P＜0.01),TIMP-2表达与对照组比较差异无显著性.回归分析显示,MVD与VEGF、VEGF/endostatin、MMP-2/TIMP-2呈明显正相关(r=0.974、0.986、0.982,P均＜0.05),与endostatin呈明显负相关(r=-0.975,P＜0.05).结论:雄激素致大鼠BPH与前列腺组织MVD增加有关,其MVD增加与血管基膜降解后血管内皮细胞增殖有关.Objective: To study angiogenesis and regulatory factors in the proliferated prostatic tissues of Sprague Dawley (SD) rats with BPH induced by testosterone. Methods: Sixteen castrated SD rats, aged 8 weeks and weighing 200~250 g, were equally randomized into a model group and a control group, and the BPH model was established by subcutaneous injection of testosterone. Immunohistochemistry and MIAS(micro-image analysis system) were used to test the manifestations of MVD(microvessel density), VEGF(vascular endothelium growth factor), flk-1, endostatin, MMP-2 (matrix metalloproteinase-2) and TIMP-2 (tissue inhibitor of metalloproteinase-2) in the prostatic tissues of both the model and the control groups. Multiple linear regression with the stepwise method was adopted to analyze the data. Results: The manifestations of MVD, VEGF, flk-1, MMP-2,MMP-2/TIMP-2 and VEGF/endostatin in the model group were higher, while that of endostatin was lower than in the control group(P< 0.01), and the manifestation of TIMP-2 showed no statistical difference between the two groups. The regression analysis indicated that MVD was positively correlated to VEGF, VEGF/endostatin and MMP-2/TIMP-2 (r= 0.974, 0.986, 0.982, P< 0.05) and negatively correlated to endostatin (r= -0.975, P< 0.05) . Conclusion: Testosterone could induce BPH in SD rats by increasing MVD and promoting the multiplication of vascular endothelial cells after regradation of basement membrane.

关 键 词：前列腺增生 血管新生 血管内皮生长因子 内皮抑素 基质金属蛋白酶 大鼠 

分 类 号：R697.33[医药卫生—泌尿科学]