去势前后大鼠腹叶前列腺显微结构的动态变化

目的：探讨去势后大鼠前列腺显微结构变化规律及机制。方法：90只大鼠分为9组,于去势后不同时间光镜、电镜下观察前列腺改变,用图像分析系统计算腺体面积与间质面积比值（G）,管腔分泌物与管腔面积比值（S）,腺体高度（H）及腺体横截面细胞数（N）。采用TUNEL法检测凋亡。免疫组化检测PCNA,计算凋亡指数（AI）和增殖指数（PI）。结果：去势后G、S、H下降,N减少。出现脂肪变、凋亡及坏死,增殖下降。结论：去势后前列腺内细胞萎缩、分泌物减少、坏死、AI升高和PI降低共同导致前列腺缩小。     

硫酸糖基化蛋白2在去势大鼠前列腺中的表达

目的 探讨硫酸糖基化蛋白2（SGP－2）在去势大腹叶前列腺表达的规律及其与前列腺凋亡的相关性。方法 将90只大鼠随机分为9组，每组10只，分别于去势后0、1、2、3、5、7、10、14、21d处死，取前列腺包埋切片后行免疫组织化学检测SGP－2和增殖细胞核抗原（PCNA),缺口末端标记术（TUNEL）和电镜检测前列腺细胞凋亡，计算阳性率，并作连续切片，行计算机图像重叠技术比较SGP－2表达与凋亡的相关性，及与PCNA表达的关系。结果 正常大鼠前列腺SGP－2表达较少，去势后则显著增加，与凋亡的变化及分布规律相似，其表达的阳性率与凋亡阳性率呈正相关（r＝0．8075，P＜0．01）。SGP－2的表达和PCNA呈负相关（r=－0．8061，P＜0．01）。结论 SGP－2在去势大鼠腹叶前列腺表达增高，与凋亡呈正相关，与PCNA呈负相关，提示可能有促凋亡和抑制增殖的作用。     

去势后大鼠腹叶前列腺微循环变化情况的观察

目的:去势后大鼠腹叶前列腺体积显著缩小,细胞凋亡,前列腺血供减少是其重要原因,但是前列腺血供减少的原因目前尚不清楚。本研究旨在探讨大鼠去势后腹叶前列腺微循环发生改变的分子机制。方法:雄性SD大鼠24只,随机分为6组,每组4只。在麻醉下行去势术(每组有1只为假手术)。然后分别于去势术后第0、1/2、1、2、3、7天,在麻醉下摘除双侧腹叶前列腺,取标本作透射电镜观察微血管,TUNEL法检测凋亡,Western印迹法检测血管内皮生长因子(VEGF)、内皮生长抑素、血管生长抑素和血管形成因子-2蛋白表达变化。结果:去势大鼠前列腺毛细血管发生了显著变化,管腔变小、关闭或破裂,内皮细胞凋亡,VEGF表达降低,内皮生长抑素、血管生长抑素表达增高,而血管形成因子-2表达无显著变化。结论:促血管因子VEGF表达下降,抑血管因子内皮生长抑素、血管生长抑素表达增高,导致血管生成和破坏平衡失调,是去势大鼠腹叶前列腺微循环发生改变的内在原因。     

雄激素对大鼠前列腺细胞凋亡与生长因子表达的影响

目的：探讨雄激素去势对大鼠前列腺侧叶LP1、LP2细胞凋亡与生长因子TGFα、KGF、bFGF、TG-Fβ1mRNA表达的影响。方法：将健康成年雄性Wistar大鼠,随机分成正常对照组、雄激素去势组及雄激素替代组。应用TUNEL法及半定量PCR方法分别检测大鼠前列腺侧叶LP1和LP2细胞凋亡及各生长因子表达变化。结果：在去势和雄激素替代治疗前后,前列腺腹、侧叶LP1的TGFβ1和TGFα表达变化,与前列腺LP1细胞凋亡、增殖密切相关;而LP1的KGF、bFGFmRNA表达与雄激素并不呈简单的正相调节关系。在侧叶,雄激素对LP2四种生长因子的表达无明显影响。结论：大鼠前列腺不同分叶的细胞对雄激素调节敏感忡与其生长因子表达的调节方式不同有关：TGFβ1和TGFα是前列腺生长调节中最重要的抑制和促分裂生长因子,KGF、hFGF可能主要参与雄激素介导的生长因子的平衡调节。     

消癃通闭对大鼠前列腺上皮细胞分裂周期的影响

目的：进一步了解中药消癃通闭对前列腺上皮细胞增殖的影响。方法：用去势Ｗｉｓｔａｒ大鼠，每天皮下注射丙酸睾酮，消癃通闭每天灌胃，于２０ｄ时断头处死，取前列腺各叶称重及测体积，取相同部位腹叶，采用流式细胞技术对大鼠前列腺上皮细胞分裂周期进行定量检测。结果：消癃通闭高剂量组的前列腺体积、腺重量及腺重与体重的比值均明显小于睾酮组，Ｐ＜００１；前列腺上皮细胞分裂Ｇ２＋Ｍ期所占比例亦明显长于睾酮组，Ｐ＜０００５。结论：消癃通闭可抑制前列腺上皮细胞的有丝分裂，从而抑制了前列腺细胞的生长     

去势后大鼠腹叶前列腺微循环的改变

目的:探讨去势后大鼠腹叶前列腺微循环的改变,及微循环的改变对前列腺细胞凋亡的作用。　方法: Sprague Dawley雄性大鼠36只,随机分为6组,一组作正常对照,其余5组分别于去势后12h、24h、72h、7d和14d 采用D95生理信号采集系统行活体微循环测量,然后再行墨汁灌注示踪微血管床变化。　结果:去势后大鼠腹叶前 列腺微循环发生显著改变,微血管密度和直径下降,流速减慢,以远端腺管最为显著。　结论:大鼠去势后前列腺微 循环的改变参与了前列腺细胞凋亡的机制,可能是前列腺“凋亡漂移现象”的机制。     

雄激素致去势大鼠前列腺增生的组织形态学研究

目的 :探讨前列腺增生大鼠前列腺的组织形态学改变。　方法 :采用SD大鼠去势后皮下注射丙酸睾酮法复制前列腺增生模型 ,用水取代法测量前列腺体积 ,苏木精 伊红染色观察前列腺增生组织结构 ,同时结合图像分析系统半定量检测前列腺增生内腺体、间质的形态计量学改变 ,并使用逐步引入剔出模型进行多元线性回归分析。结果 :与正常对照组比 ,模型组前列腺体积明显增大 (P <0 .0 1) ,腺腔扩张、间质增多 ;腺体面积、腺体相对总体积、单位体积内腺体平均直径、平均体积、平均表面积均明显增高 (P <0 .0 1) ,腺体数目、腺体数密度、腺体表面积 /腺体体积、腺体平均曲率显著减少 (P <0 .0 5～ 0 .0 1) ,体积密度无差异 ;间质面积明显减少 (P <0 .0 1) ,但间质相对总体积明显增加 (P <0 .0 5 )。回归分析结果 ,前列腺体积与腺体相对总体积和间质相对总体积呈明显正相关 (r分别为 0 .989和 0 .789,P均 <0 .0 0 1) ;前列腺体积与腺体平均体积呈明显正相关 (r =0 .82 4 ,P <0 .0 0 1)。　结论 :雄激素致去势大鼠前列腺增生以腺上皮增生为主 ,表现为腺腔的扩张 ,同时伴间质组织的增生     

前列舒通对丙酸睾酮诱导的去势大鼠前列腺增生的作用机制

目的探讨前列舒通抑制良性前列腺增生的治疗作用机理,观察其对良性前列腺增生的治疗效果。方法观察前列舒通作用于丙酸睾酮诱导去势大鼠前列腺增生模型后的前列腺指数,前列腺体积,前列腺腺体总面积、bFGF(碱性成纤维生长因子)、EGF(表皮生长因子)、bcl-2(抑制细胞凋亡因子),以及前列腺组织病理学改变。结果前列舒通各浓度组前列腺指数、前列腺体积、前列腺腺体总面积、bFGF、EGF、bcl-2均明显低于模型组。结论前列舒通能显著抑制丙酸睾酮诱导去势大鼠的良性前列腺增生,其机制可能是通过降低bFGF、EGF、bcl-2的表达水平,从而抑制前列腺细胞增殖和促进凋亡而实现的。     

去势后阻断自噬对大鼠前列腺细胞凋亡的影响

目的：探讨去势后阻断自噬对大鼠前列腺细胞凋亡的影响。方法 SD雄性大鼠72只随机分为3组：即假切对照组、去势组、去势＋硫酸羟氯喹处理组。各组大鼠分别于术后第1、3、7、10、14、21d随机抽取4只,完整取出前列腺组织。 HE染色观察大鼠前列腺组织形态学变化,电镜下观察前列腺微观结构、自噬和凋亡的变化,免疫组化SP法检测自噬受体蛋白P62和凋亡促进蛋白 Caspase－3在前列腺组织中表达。结果光镜下去势后大鼠前列腺体积逐渐缩小,腺上皮细胞逐渐萎缩,核染色加深,腺泡萎缩甚至闭塞,间质增生,加用羟氯喹处理后这一变化更加明显。电镜下观察去势后自噬小体的数量明显增加。免疫组化检测去势后自噬活性蛋白P62表达减弱,用羟氯喹处理后表达增强;凋亡促进蛋白 Caspase－3表达增强,用羟氯喹处理后表达进一步增强。结论去势后大鼠前列腺细胞自噬增加,自噬抑制剂羟氯喹可通过阻断细胞自噬增加大鼠细胞凋亡,自噬可能具有抗凋亡作用。     

桂枝对大鼠良性前列腺增生细胞增殖和凋亡的影响

目的：研究桂枝对大鼠良性前列腺增生细胞增殖和凋亡的影响。方法：大鼠皮下注射丙酸睾丸素（5mg/kg）造成良性前列腺增生动物模型,经灌胃给以不同剂量桂枝水煎液（6.67g/kg、3.33g/kg和1.67g/kg）,阳性对照组相同途径给予保列治（非那雄胺）水溶液（0.45mg/kg）,正常对照组和模型组给予等体积离子净化水。30d后处死大鼠,观察大鼠前列腺指数变化,HE染色光镜观察前列腺病理改变,Ki-67免疫组化染色和TUNEL染色检测大鼠前列腺细胞的增殖指数和凋亡指数。结果：桂枝能明显降低大鼠的前列腺指数（P〈0.01）,明显减轻前列腺组织病理改变,提高前列腺细胞凋亡表达率（P〈0.01）;而对前列腺细胞增殖指数没有明显作用（P〉0.05）。结论：桂枝具有抗大鼠良性前列腺增生的作用,促进大鼠前列腺增生细胞凋亡可能是其机理之一。     

雄激素对大鼠腹叶前列腺GDNF mRNA表达的影响

目的 :探讨雄激素对大鼠腹叶前列腺中胶质细胞源性神经营养因子 (GDNF)mRNA表达的影响。　方法 :2 4只SD大鼠分为 3组 ,其中A组 (n =8)为假手术对照组 ,B组 (n =8)为去势组 ,C组 (n =8)为雄激素替代组 (去势后肌注十一酸睾酮 5 0mg/kg) ;术后 3d处死 ,通过半定量RT PCR检测GDNFmRNA在去势前后和雄激素替代组大鼠腹叶前列腺中的表达变化。　结果 :去势后大鼠前列腺的体积萎缩变小 ;雄激素替代组出现前列腺增生变大 ;对照组正常的大鼠前列腺有GDNFmRNA表达 ,去势组GDNFmRNA表达量减少 ,雄激素替代组GDNFmRNA表达量增加。与正常对照组比较 ,去势组的GDNFmRNA表达量显著减少 (P <0 .0 5 ) ,雄激素替代组的GDNFmRNA表达量显著增加(P <0 .0 5 )。　结论 :雄激素可增加GDNFmRNA表达 ,促进前列腺细胞生长。     

雄激素对良性前列腺增生组织中Bcl-2 mRNA表达的影响

目的 研究雄激素水平对良性前列腺增生（ＢＰＨ）组织中凋亡抑制基因Ｂｃｌ－２ ｍＲＮＡ表达的影响。方法 分别通过服用药物和切除睾丸改变ＢＰＨ患者和大鼠机体雄激素水平,采用ｍＲＮＡ斑点杂交技术,检测不同雄激素水平下的ＢＰＨ组织和大鼠前列腺组织Ｂｃｌ－２ ｍＲＮＡ的表达情况。结果 在所有２０例人ＢＰＨ组织中,Ｂｃｌ－２ ｍＲＮＡ表达均呈阳性,未服药对照组Ｂｃｌ－２ ｍＲＮＡ杂交斑点和积分光密度值（ＩＯＤ     

Antagonistic effect of androgen on prostatic cell death

Androgen, besides having the well-established agonistic ability to stimulate prostate cell proliferation, also has an antagonistic ability to inhibit prostatic cell death. This statement is based upon the observations that 1) only 2.1% of the total prostatic cells die per day when serum testosterone level is sufficient for chronic maintenance of the gland; 2) 3 days following castration, when serum testosterone level is less than 10% of the intact value, the percentage of total prostatic cells now dying per day is increased tenfold to a value of 20.8%; and 3) this high rate of prostatic cell death can be inhibited following castration if serum androgen level is appropriately maintained by exogenous testosterone treatment. The serum testosterone level needed to antagonistically inhibit prostatic cell death (ie, 1.4 +/- 0.1 ng/ml) is more than twofold lower than that needed to antagonistically stimulate prostatic cell proliferation (3.3 +/- 0.4 ng/ml). Due to this dose difference, it is experimentally possible in castrated rats to inhibit prostatic cell death selectively without simultaneously stimulating cell proliferation and still completely prevent the rapid involution of the prostate following castration. These results suggest that the rapid involution of the prostate following castration is predominantly due to a decreased antagonistic effect of androgen on prostatic cell death rather than to a decreased agonistic effect of androgen on prostatic cell proliferation and that these two androgenic effects are distinct processes in the prostate.     

缺氧诱导因子-1α在去势前后大鼠腹叶前列腺中表达的变化

目的探讨与缺氧相关的缺氧诱导因子-1α(HIF-1α)是否参与去势后前列腺萎缩过程.方法24只SD大鼠分为3组,其中A组(n=8)为假手术对照组,B组(n=8)为去势组,C组(n=8)为雄激素替代组(去势后肌注十一酸睾酮50mg/kg);术后3天处死,通过半定量RT-PCR检测与HIF-1α在去势前后前列腺表达变化.结果去势后大鼠前列腺的体积萎缩变小;雄激素替代组出现前列腺增生变大;对照组正常的大鼠前列腺有HIF-1 α mRNA低水平表达,去势组HIF-1α mRNA表达量增加,雄激素替代组HIF-1αmRNA表达量减少,与正常对照组比较,去势组的HIF-1α mRNA的表达量显著增加(P＜0.05),雄激素替代组的HIF-1αmRNA的表达量显著减少(P＜0.01).结论前列腺组织的缺氧参与去势后大鼠前列腺的早期萎缩过程.     

Effects of finasteride and bicalutamide on prostatic blood flow in the rat

OBJECTIVE: To determine whether finasteride and bicalutamide, both currently used in the clinical management of patients with prostate diseases because they have anti-androgenic properties, have any effects on prostatic blood flow in a rat prostate model, as androgens are known to be involved in the regulation of prostatic blood flow and angiogenesis. MATERIALS AND METHODS: Both finasteride and bicalutamide were supplied as oral suspensions in water and given daily to rats for 7 days by tube feeding. Blood flows to the ventral and dorsal prostates, and to the kidneys, were measured using the radioactive microsphere technique. In the bicalutamide experiments, some rats were treated with the Leydig cell toxin ethane dimethane sulphonate (EDS), to obtain a castration-like effect, and one group of these rats received testosterone. RESULTS: Finasteride induced a clear decrease in blood flow to the ventral and dorsal prostates after 7 days of treatment, with no significant changes in blood pressure or kidney blood flow. Bicalutamide inhibited the testosterone-induced increment of prostatic blood flow observed in EDS-treated animals. CONCLUSIONS: Finasteride, a blocker of 5alpha-reductase, decreases prostate blood flow after 7 days of administration. The response was slower than that after castration, but was of similar magnitude. Blood flow was also decreased after treatment with the androgen-receptor inhibitor bicalutamide. These observations suggest that prostatic blood flow is increased by dihydrotestosterone, and that the androgen receptor is responsible for mediating this effect.     

Potentiating Effect of Buserelin Acetate, an LHRH Agonist, on the Proliferation of Ventral Prostatic Epithelial Cells in Testosterone-Treated Castrated Rats

Background: We used buserelin acetate ([D-Ser(But)6] LHRH), an LHRH agonist and strong blocker of LH secretion, as a treatment for prostatic cancer. It is possible that this LHRH agonist has a proliferative effect on the prostate in addition to suppressing LH secretion. The purpose of this study was to examine the proliferative effect of LHRH agonist on rat prostatic epithelial cells.
Methods: We determined the optimal dose of testosterone necessary to maintain a positive level of proliferating cell nuclear antigen (PCNA) in the ventral prostatic epithelial cells of castrated Wistar rats. Testosterone-treated rats then received various doses of buserelin acetate. Castrated rats without exogenous testosterone also received buserelin acetate. The PCNA positivity was determined by immunohistochemistry with anti-PCNA monoclonal antibody.
Results: The optimal dose of testosterone enanthate was 4mg at 0 and 28 days after castration. Administration of buserelin acetate on day 0 and 28 in doses of 0.1 6mg to 1.28mg significantly increased PCNA positivity in a dose-dependent manner. Administration of buserelin acetate to castrated rats without testosterone also increased PCNA positivity but there was no statistical significance. Conclusions: Buserelin acetate has a potentiating effect on the proliferation of ventral prostatic epithelial cells of castrated rat in the presence of a physiological level of exogenous testosterone. This effect may slightly influence the result of hormonal therapy by LHRH agonist.     

Testosterone-induced decrement of prostatic vascular resistance in rats is reversed by estrogens

The function and growth of the rat prostate are stimulated by androgens and inhibited by estrogens. To study the influence of these hormones on the prostatic blood flow, prostatic vascular resistance was measured in castrated adult rats, which were testosterone supplemented and treated with different estrogenic substances. Prostatic blood flow was measured using the microsphere technique. Testosterone supplementation for 8-9 days after castration resulted in decreased vascular resistance in both the ventral and dorsolateral prostates. In testosterone-supplemented rats, treatment for the same period of time with estradiol benzoate, ethinyl estradiol, and diethylstilbestrol induced increased vascular resistance in both the ventral and dorsolateral prostates. However, treatment with estromustine or estramustine did not change prostatic vascular resistance significantly. It was concluded that the testosterone-induced decrease of prostatic vascular resistance was reversed by estradiol, ethinyl estradiol, and diethylstilbestrol, possibly by a direct effect on the prostate.