极低水平雄激素动物模型构建及其对前列腺细胞生长的影响

Establishment of extremely low level of androgen rat model and the effect on the growth of prostate tissue in vivo

目的 构建去势大鼠双侧肾上腺大网膜自体种植模型,研究其对体内不同激素的影响,进一步探讨不同激素水平下前列腺组织的变化情况. 方法 2011年4月至2013年5月,利用随机数字表法将32只雄性成年SD大鼠随机分成4组（每组8只）,即去势＋肾上腺大网膜自体种植组（A组）、单纯去势组（B组）、单纯肾上腺大网膜自体种植组（C组）及对照组（D组）,其中A、C组术中移植物周围滴80μl促肾上腺皮质激素.术后7周检测各组大鼠门静脉、下腔静脉血中睾酮、皮质醇、醛固酮水平,以及前列腺匀浆中双氢睾酮的水平.采用免疫组化方法研究各组大鼠前列腺组织相关蛋白的变化.分析睾酮及双氢睾酮与前列腺相关蛋白表达之间的相关性. 结果 A组门静脉[（0.19±0.04） nmol/L]与下腔静脉[（0.02±0.01） nmol/L]血睾酮水平比较差异有统计学意义（P＜0.01）.A、B组血清睾酮水平分别为（0.02±0.01）、（0.42±0.40）nmol/L,差异有统计学意义（P＜0.05）.不同分组及不同静脉间的血清醛固酮及皮质醇水平比较差异均无统计学意义（P＞0.05）.A、B组前列腺匀浆双氢睾酮水平分别为（2.76±0.93）、（35.11±13.61）nmol/L,差异有统计学意义（P＜0.05）.与B组相比,A组所构建的体内极低雄激素水平模型能显著降低前列腺上皮细胞的Bcl-2及Ki-67表达.前列腺上皮细胞中Ki-67表达水平及Bcl-2/Bax比值与血清睾酮及前列腺双氢睾酮水平成正相关（P＜0.01）. 结论 本研究通过构建去势大鼠双侧肾上腺大网膜自体种植模型,证实肝脏对雄激素的灭活作用,且不影响体内皮质醇及醛固酮正常水平,进一步发现体内极低雄激素水平下前列腺细胞增殖明显受到抑制.

[ Abstract] Objective To establish the rat model of extremely-low level of androgen and to observe the change of the prostate under such status. Methods Thirty-two rats were divided into 4 groups random- ly （8 for each group）. Blood samples were collected from the portal vein and postcava after planned opera- tions. Serum testosterone, cortisol, aldosterone and dihydrotestosterone were detected according to the rela- tive protocols. Immunohistochemical staining of prostate tissue and correlation analysis were also conducted. Results A significant statistical difference was detected between serum testosterone in portal vein （0.19± 0.04 nmol/L） and postcava （0.02±0.01 nmol/L） in emasculation plus self-implantation group （P〈0.01）. Testosterone was significantly different between with and without adrenal gland self-implantation after emas- culation （P〈0.05）. No significant difference of eortiso] and aldosterone was detected in our analyses （P〉0.05）. The extremely-low level of serum androgen had a more notable effect on Bcl-2 and Ki-67 down-regu- lation compared to simply emasculation. A positive correlation was detected between the expression of Ki-67, Bcl-2/Bax and the serum level of testosterone and dihydrotestosterone （P〈0.05）. Conclusion Adrenal gland self-implantation in greater omentum on rats after emasculation could maintain the level of serum an- drogen at an extremely-low level, which could better inhibit the proliferation of prostatic cells without affect- ing the normal serum cortisol and aldosterone.