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。     

去势前后大鼠腹叶前列腺形态学的动态改变

目的：探讨去势前后大鼠腹叶前列腺形态学和组织学的变化规律，以及引起这种变化的机制。方法：将90只SD系成年雄性大鼠分为9组，其中一组作为正常对照，其余8组去势后分别于术后第1、2、3、5、7、10、14、21天处死，测血清雄激素浓度（T），腹叶前列腺的重量、体积和密度。再行石蜡包埋切片，HE染色，采用计算机图像分析系统计算腺体面积与间质面积之比值（G）、管腔分泌物与管腔面积这比值（S）、腺细胞高度（H）及单个腺体模截面细胞数（N）。TUNEL检测细胞凋亡，免疫组织化学方法测定增殖抗原PCNA。结果：去势后T急剧下降，前列腺重量和体积进行性减小，而密度先稍降低再逐渐升高。G、S、H、N均减小。腺上皮细胞凋亡、坏死，增殖下降。结论：去势后大鼠腹叶前列腺重量和体积的减小，可能是由于细胞数目减少、细胞萎缩、细胞分泌物减少等综合作用的结果，其始动因素可能是T水平的降低。     

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。     

前列腺增生症和前列腺癌的前列腺组织微循环改变

目的 探讨前列腺微循环在前列腺病理变化中的作用.方法 取前列腺增生症 (BPH) 未服非那雄胺者标本 (简称BPH组) 30例和服用非那雄胺标本 (简称BPHF)10例,正常前列腺标本 (简称NP组)5例,前列腺癌标本(简称PCa组)标本10例,H.E.切片,采用WX-6B型BIU-2000微循环图像处理系统分析间质面积与腺体面积的比值(S/G),正常腺体与萎缩腺体面积的比值 (N/A);CD34免疫组化显示微血管,检测平均微血管密度 (MVD)、间质内平均微血管密度 (SMVD)、正常腺体微血管密度 (NMVD)和萎缩腺体微血管密度 (AMVD).PSA免疫组化测灰度值.分别比较上述各组各指标的差异.结果 BPH组、BPHF及PCa组S/G、MVD高于NP组,BPH、BPHF组N/A和PSA灰度值低于NP组(P＜0.01),BPHF与BPH组比较,S/G、N/A及SMVD降低,PSA灰度值升高 (PSA表达降低) (P＜0.01).相关分析提示,PSA与S/G和SMVD都呈正相关性.结论 前列腺组织内局部微循环与前列腺病理改变密切相关.间质微血管增多可能是前列腺问质增生的原冈之一,PSA可通过影响腺体和间质内微循环而发挥刺激增生作用.非那雄胺可通过降低PSA及组织内微循环而发挥抑制前列腺增生的作用.     

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.     

去势前后犬前列腺的动态病理学改变

采用光镜、电镜、原位末端标记法，连续观察去势前后犬前列腺的病理学改变。去势后犬前列腺的病理改变可划分为新鲜凋亡期和陈旧凋亡期。去势不仅导致前列腺细胞的凋亡病变，还引起萎缩、坏死病变。此三种病变在前列腺上皮和基质内都存在，共同构成了去势晚期前列腺结构和功能的高度损害。     

前列腺摘除术与去势术前后雄激素变化的研究

目的探讨和研究前列腺摘除术与去势术对血清中雄激素(T、FT、DHT)的变化。方法39例研究对象,其中23例前列腺摘除术,16例去势术在手术前后分别采集血清样本,用放射免疫法测定血清中T、FT、DHT浓度。结果 前列腺摘除术后血清中T、FT、DHT分别较术前下降34.45％,33.53％,50.41％;去势术后血清中T、FT、DHT分别较术前下降92.27％,92.26％,58.36％。两种手术前后血清中T、FT、DHT的变化都有显著的统计学意义(P<0.001)。结论 前列腺摘除术后血清中雄激素会发生明显的变化,以DHT改变为显著。而去势术能够去除绝大部分T、FT,而DHT仅下降58.36%,在雄激素依赖的前列腺癌病例应当继续使用雄激素受体竞争剂,阻止残存的雄激素作用。     

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。     

去势对雄性大鼠血管成形术后再狭窄的影响

目的 :系统观察血管外膜细胞在血管成形术 (PTA)后再狭窄过程中的动态变化 ,通过复制去势模型对照观察雄激素对再狭窄的影响 ,并探讨其作用机制。　方法 :复制雄性SD大鼠的去势模型及颈总动脉再狭窄模型 ,于术后 3、7、14、2 8d不同时间点取材 ,行苏木精 伊红染色及免疫组化染色 ,并以电镜观察血管狭窄情况。　结果 :PTA术后 3d增殖细胞首先出现在血管外膜 ,并发生表型转变 ,术后 7d时外膜细胞增殖最明显 ,并向内膜迁移 ,术后 14d外膜细胞增殖减少 ,增殖细胞集中于中膜及新生内膜。各观察时间点 ,去势雄性大鼠的血管外膜面积、新生内膜面积、血管狭窄程度 ,均较未去势组大。以 14d组为例 ,血管外膜面积 [(35 6 6± 337) μm2 vs (2 75 1± 4 0 1) μm2 ,P =0 .0 0 8],新生内膜面积 [(35 5 3± 4 77) μm2 vs (2 75 7± 4 35 ) μm2 ,P =0 .0 2 5 ],血管狭窄程度 [(76± 2 ) %vs (6 0±8) % ,P =0 .0 0 5 ],外膜细胞增殖指数 [(2 9± 2 ) %vs (13± 1) % ,P <0 .0 0 1]。　结论 :PTA术后血管外膜细胞增殖、迁移参与了再狭窄的形成。生理状态下体内雄激素可以减轻血管再狭窄程度 ,其作用机制可能与干预血管外膜细胞活化有关。     

手术去势对前列腺癌患者血脂代谢的影响

目的：探讨前列腺癌患者去势手术后雄激素水平降低及对血脂代谢的影响。方法：对诊断明确的36例进展期前列腺癌患者行双侧睾丸切除术,分别于术前、术后1、3、6个月及1年测定血清睾酮（T）、游离睾酮（FT）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白A1（APO-A1）、载脂蛋白B（APO-B）。结果：去势术后1个月,T、FT较术前明显降低（0．45±0．05ng／mlVS4．88±0．21ng／ml,P〈0．01;2．09±0．56pmol／I。VS35．25±4．20pmol／I,,P〈0．01）,以后持续下降,术后6个月降至最低。TG于术后1个月开始较术前显著升高（1．88±0．28mmol／L,VS1．38±0．20mmol／L,P〈0．01）。FC、LDL-C于术后3个月开始较术前明显升高（5．29±0．7lmmol／L VS3．6l±0．59mmol／L,P〈0．01;3．13±0．44mmol／L VS1．72±0．26mmol／L,P〈0．01）,以后呈继续上升趋势。HDL-C于术后3个月开始较术前明显降低（1．47±0．28rnmol／L VS1．86±0．24mmol／L,P〈0．01）。APO-A1、APO—B在手术前后无明显变化。结论：前列腺癌患者去势手术后,随着雄激素水平的降低,出现血脂代谢异常,TG、TC、LDL-C升高,HDL-C降低,可能使相关心血管疾病的发生率增加。     

Cell proliferation and apoptosis in prostate tumors and adjacent non-malignant prostate tissue in patients at different time-points after castration treatment

BACKGROUND: Androgen ablation is the standard treatment for advanced prostate cancer but the short-term cellular effects are largely unknown. METHODS: Sextant prostate biopsies were taken from 77 prostate cancer patients before and 1-10 days after castration treatment. Apoptosis, cell proliferation, and morphology were studied in malignant and non-malignant tissue, using stereological and immunohistochemical methods. RESULTS: Epithelial cell proliferation was significantly decreased both in non-malignant and malignant epithelium already 1 day after therapy. It remained low until day 7, but increased thereafter in the remaining non-malignant epithelial cells and in some tumors. Epithelial cell apoptosis was significantly increased during the first week and then returned to basal levels. The maximal apoptotic indexes, seven- and two-times the intact levels in the non-malignant and malignant glands, respectively, were found at days 3-4 or even earlier in the tumors. Signs of tumor shrinkage such as glandular collapse and decreased tumor cell size were observed from day 3 in most tumors. DISCUSSION: The present study shows that the magnitude and kinetics of the response to castration in the normal human prostate is very similar to the response previously described in rodents. We also demonstrate that most human prostate tumors rapidly respond to castration indicating the need for further evaluation of when and how to best monitor the effects of hormone ablation therapy in prostate cancer patients.     

Castration triggers growth of previously static androgen-independent lesions in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model

BACKGROUND: Androgen-deprivation remains the standard of care for metastatic prostate cancer, yet its total impact on the course of disease is incompletely established. METHODS: We have examined the long-term effects of castration upon the progression of established cancer in the TRAMP transgenic mouse model of prostate cancer. Mice castrated at 15-weeks of age, as well as intact littermates, were followed until spontaneous death from cancer. RESULTS: Statistical analyses of age-at-death versus primary tumor mass revealed that mice segregate into two categories of response to androgen-deprivation. In Category One, the act of castration paradoxically triggers the growth of microscopic androgen-independent lesions, as evidenced by a statistical synchronization of primary tumor growth. Delaying castration until 20-weeks of age delays the synchronized growth of these tumors, as well as the deaths of the host mice. In Category Two, castration eliminates or substantially delays primary tumor growth, but fails to eliminate metastases. so that castration is found to impart no long-term survival advantage. CONCLUSIONS: We propose a two-step model for the alteration of androgen signaling in prostate cancer capable of explaining the above paradoxical results, which is based upon the dualistic role of androgens as both survival and differentiation factors. This model makes specific predictions for clinical intervention that are discussed in light of published studies.     

Effect of Castration on Lectin Staining in Rat Epididymis

Seven rhodamine-conjugated lectins (PNA, RCA I, Con A, WGA, UEA I, SBA, DBA) were used to follow the staining pattern of the rat epididymis at different time points after castration. The affinity of the intratubular sperm mass for the lectins increased rapidly with concurrent augmentation of the staining in the principal cells but a decline of the reaction in the light cells. The light cells showed some differences in their response to castration, which was compatible with secretory/absorptive activity in caput and absorptive activity in cauda. The active phase of sperm mass destruction and epithelial involution was accompanied by local accumulation of macrophages and round cells, which also acquired an increased affinity for most of the lectins. It is concluded that the androgen-deprived epididymis is rapidly programmed for autolytic and phagocytic processes, which include the destruction of macromolecules including glycoproteins of the spermatozoa.     

手术去势对前列腺癌患者胰岛素抵抗及释放节律的影响

目的：探讨前列腺癌患者手术去势后,雄激素水平降低对机体胰岛素抵抗及胰岛素释放节律的影响.方法：36例患者经前列腺穿刺,病理诊断为前列腺癌,Gleason评分7～9分,临床分期Ⅲ～Ⅳ期,行双侧睾丸切除,术前无Ⅱ型糖尿病史.术前、术后1个月、3个月、6个月及1年分别测定血清睾酮（T）,血清游离睾酮（FT）,空腹及餐后0.5 h、1 h、2 h、3 h胰岛素.空腹及餐后0.5 h、1 h、2 h、3 h血糖.计算胰岛素抵抗指数及绘制胰岛素释放曲线.结果：本组患者去势术后1个月血清T、FT较术前显著下降[（0.45±0.05）ng/ml vs.（4.88±0.23）ng/ml,P〈0.001;（2.07±0.19）pmol/L vs.（35.10±4.37）pmol/L,P〈0.001].此后继续下降,术后6个月左右达到最低,并维持低水平.空腹血糖、空腹胰岛素、餐后2 h血糖及胰岛素于术后1个月显著升高[（5.63±0.78）mmol/L vs.（5.11±0.21）mmol/L,P〈0.05;（10.48±3.68）μU/ml vs.（7.56±2.58）μIU/ml,P〈0.05;（6.66±0.72）mmol/L vs.（5.78±0.33）mmol/L,P〈0.01;（16.31±0.45）μIU/ml vs.（13.21±0.35）μIU/ml,P〈0.01）],此后仍呈上升趋势,胰岛素释放曲线示餐后0.5 h峰值低于空腹时5倍或峰值后移.胰岛素抵抗指数（空腹胰岛素×空腹血糖÷22.5）术后1个月开始显著升高（2.62±0.13 vs.1.72±0.02,P〈0.05）（HOMA法,稳定模型法）,此后呈上升趋势.结论：双侧睾丸切除后,雄激素水平下降而导致胰岛素抵抗增加,且胰岛素释放曲线峰值下降或后移.Ⅱ型糖尿病发生风险显著增加.     

Perioperative Changes in the Microcirculation in Feet After Foot and Ankle Surgery

The senior author (N.P.G.) observed that if the foot became dependent in the first 48 hours after foot surgery, the patient had swelling and pain. This effect seemed less after about 48 hours. The authors set out to see if there was a scientific basis for this. Laser Doppler was used to assess blood flow in 14 patients. Flow was recorded in the big toe, at heart level, and on dependency, preoperatively and postoperatively. Postural vasoconstriction was calculated, and time for blood flow to normalize was recorded. Mean postural vasoconstriction preoperatively was 51.31%; postoperative mean at 24 hours was 23.05%, at 48 hours 36.62%, and at 72 hours 44.24%. There was a difference between the preoperative levels and the 24-, 48-, and 72-hour postoperative levels (P < .05). Results showed that it takes longer than 72 hours rather than 48 hours for microcirculation to return to normal. The results emphasized the importance of postoperative foot elevation for at least 48 hours because of this phenomenon.     

Vas Deferens and Seminal Vesicles Epithelium after Castration: a SEM Study

Vas deferens und Samenbläschen-Epithel nach der Kastration: Eine Rasterelektronenmikroskopische Untersuchung
Mittels der Rasterelektronenmikroskopie wurden die Auswirkungen der Orchidektomie auf das Vas deferens und das Samenbläschenepithel von 20 erwachsenen Albinoratten untersucht. Die innere Oberfläche des Vas deferens der kastrierten Ratte zeigte eine Reduktion der Höhe und der Verdickung der Mukosafalten, sowie an der Zellspitze eine beträchtliche Abnahme der Mikrovilli und das Verschwinden der sekretorischen Bläschen.
Bei den Samenbläschen bewirkte die Kastration ebenfalls eine Abflachung der Mukosafalten und eine Reduktion der Mikrovilli an den apikalen Zellstrukturen; ebenfalls verschwanden die Sekretionsgranula. Diese Veränderungen liefern den Beweis einer Abnahme der Absorptionskapazität und einer Suppression der sekretorischen Aktivität dieser Epithelien als eine Folgerung aus dem Abfall der Androgenwerte.