前列冲剂对前列腺增生大鼠血清酸性磷酸酶及T和E_2的影响

目的观察前列冲剂对前列腺增生大鼠血清前列腺特异性酸性磷酸酶活性和性激素水平的影响。方法50只SD雄性大鼠中,10只为正常对照组用蓖麻油造模。其余40只中,10只为模型组,另30只为实验组,给他们皮下注射丙酸睾丸酮(4ml/kg)诱导前列腺增生,实验组(分低、中、高剂量组)每天分别给予不同剂量前列冲剂(2.5ml/kg,5ml/kg,10ml/kg)灌胃。5周后将大鼠处死,摘取前列腺,称体重及前列腺湿重,计算前列腺指数;测定大鼠血清睾酮(T)、雌激素(E2)、总酸性磷酸酶(ACP)、非前列腺特异性酸性磷酸酶(NPAP),并计算前列腺特异性酸性磷酸酶(PAP)。结果中剂量和大剂量前列冲剂明显降低血清PAP,与模型组比较差异显著(P<0.01);明显拮抗实验性前列腺增生大鼠血清T水平升高(P<0.01),对血清E2水平无明显影响。中剂量(5ml/kg)和大剂量(10ml/kg)前列冲剂可以明显减少前列腺湿重和减小前列腺指数。结论前列冲剂有明显降低实验性前列腺增生模型大鼠血清PAP的作用,可以明显拮抗血清T水平的升高。前列冲剂抑制良性前列腺组织增生的作用与血清性激素水平变化有关。     

Effects of mepartricin on estradiol and testosterone serum levels and on prostatic estrogen, androgen and adrenergic receptor concentrations in adult rats.

The effects induced by oral administration of 0, 5 and 20 mg of meparticin kg(-1)of body weight for 28 days (group 1, 2 and 3, respectively) upon prostatic estrogen, androgen, alpha(1)- and beta-adrenergic receptor concentrations and on estradiol and testosterone serum levels in adult male rats were studied. The effects produced by mepartricin treatments on the weight and dimension of the gland were investigated. Both mepartricin dosages induced significant decreases (P< 0.05) of the absolute and relative weights and of the dimensions of the prostate. A significant dose-dependent decrease (P< 0.05) in estradiol serum levels was observed in treated rats, whereas no significant modifications were found in testosterone serum levels. As far as prostatic steroid receptor concentrations were concerned, a significant (P< 0.05) decrease in estrogen receptor number was observed in both treated groups, whilst a significant increase (P< 0.05) of androgen receptor concentrations was recorded only in rats treated with 20 mg mepartricin kg(-1). Conversely, a dose-dependent up-regulation of both prostatic alpha(1)- and beta-AR was found. Data obtained suggest that the prostatic alpha(1)-AR expression may be strongly influenced by estrogen deprivation (mepartricin treatment), therefore the combination of estrogen suppression (mepartricin) and adrenergic suppression (alpha(1)-AR blockers) may be suggested as a possible pharmacotherapeutic strategy for the treatment of benign prostatic hyperplasia.     

GSK3β抑制剂氯化锂对大鼠前列腺增生的影响

目的：探讨 GSK3β抑制剂氯化锂在大鼠前列腺增生治疗中的作用。方法通过皮下注射丙酸睾酮的方法复制前列腺增生模型,建模大鼠随机分成3组：氯化锂高剂量治疗组、低剂量治疗组和模型对照组,另设正常对照组。高剂量和低剂量治疗组分别以20mg／（ kg· d）、10mg （kg· d）的剂量腹腔注射氯化锂,连续给药30d。称量各组大鼠前列腺组织湿重、体积,计算前列腺指数;酶联免疫法测定血清中睾酮（T）、雌激素（E2）和性激素结合球蛋白（SHBG）含量。结果氯化锂治疗组的前列腺湿重、体积和脏器系数较模型对照组显著降低（P＜0．01）;氯化锂治疗组的T、E2和SHBG水平也较模型对照组降低（P＜0．05）。结论 GSK3β抑制剂氯化锂对前列腺增生具有一定抑制作用。     

相对缺血缺氧与丙酸睾酮在促进前列腺增生作用中的相互关系

目的 研究相对缺血缺氧状态和丙酸睾酮作用于大鼠时大鼠前列腺组织中Caspase3的表达及前列腺指数,了解缺血缺氧状态与雄激素对促进前列腺增生作用的相互关系.方法 应用免疫组化方法检测60例大鼠前列腺组织中Caspase-3的表达,并测定每只大鼠前列腺指数PI值,将相对缺血缺氧与丙酸睾酮同时作用于大鼠的前列腺组织与二者单纯作用于大鼠的前列腺组织进行比较.结果 相对缺血缺氧与丙酸睾酮同时作用于大鼠时前列腺组织中Caspase-3的表达低于二者单独作用于大鼠时前列腺组织中Caspase-3的表达,差异有统计学意义.相对缺血缺氧与丙酸睾酮同时作用于大鼠时前列腺指数PI值与二者单独作用于大鼠时前列腺组织PI值比较.差异有统计学意义.结论 相对缺血缺氧与丙酸睾酮同时作用比各自单独作用时更能促进前列腺增生,提示相对缺血缺氧与丙酸睾酮在促进前列腺良性增生方面可能有相加或协同作用.     

白花败酱草提取物对小鼠前列腺增生的实验研究

目的 研究白花败酱草提取物（PVJE）对小鼠前列腺增生的抑制作用.方法 小鼠随机分为对照组、模型组、普乐安组、小剂量PVJE组、大剂量PVJE组.对照组皮下注射花生油溶液0.1 ml/只,其余各组均皮下注射丙酸睾酮溶液5mg（kg·d）,同时普乐安组给予5 g/（kg·d）的普乐安溶液灌胃,小剂量PVJE组、大剂量PVJE组分别给予0.02、0.04g/（kg·d）的白花败酱草提取物溶液灌胃,共给药12d.研究小鼠前列腺湿重、前列腺指数、性激素水平和光镜下前列腺形态学的变化.结果 与模型组比较,PVJE能明显抑制由丙酸睾丸酮诱发的小鼠前列腺增生,小鼠血清睾丸酮（T）、和雌二醇（E2）含量明显降低.结论 PVJE对丙酸睾丸酮所致小鼠前列腺增生具有显著的拮抗作用.     

Urinary analysis of four testosterone metabolites and pregnanediol by gas chromatography-combustion-isotope ratio mass spectrometry after oral administrations of testosterone

The most frequently used method to demonstrate testosterone abuse is the determination of the testosterone and epitestosterone concentration ratio (T/E ratio) in urine. Nevertheless, it is known that factors other than testosterone administration may increase the T/E ratio. In the last years, the determination of the carbon isotope ratio has proven to be the most promising method to help discriminate between naturally elevated T/E ratios and those reflecting T use. In this paper, an excretion study following oral administration of 40 mg testosterone undecanoate initially and 13 h later is presented. Four testosterone metabolites (androsterone, etiocholanolone, 5 alpha-androstanediol, and 5 beta-androstanediol) together with an endogenous reference (5 beta-pregnanediol) were extracted from the urines and the delta(13)C/(12)C ratio of each compound was analyzed by gas chromatography-combustion-isotope ratio mass spectrometry. The results show similar maximum delta(13)C-value variations (parts per thousand difference of delta(13)C/(12)C ratio from the isotope ratio standard) for the T metabolites and concomitant changes of the T/E ratios after administration of the first and the second dose of T. Whereas the T/E ratios as well as the androsterone, etiocholanolone and 5 alpha-androstanediol delta(13)C-values returned to the baseline 15 h after the second T administration, a decrease of the 5 beta-androstanediol delta-values could be detected for over 40 h. This suggests that measurements of 5 beta-androstanediol delta-values allow the detection of a testosterone ingestion over a longer post-administration period than other T metabolites delta(13)C-values or than the usual T/E ratio approach.     

盐酸小檗碱对丙酸睾酮诱导的前列腺增生小鼠的作用及其机制研究

目的研究盐酸小檗碱对丙酸睾酮诱导的前列腺增生小鼠的作用及其机制。方法使用丙酸睾酮诱导建立前列腺增生小鼠模型,造模成功后,选择雄性昆明小鼠40只,随机分为4组,分别为模型组(生理盐水组)、盐酸小檗碱低剂量(10 mg/ml)组、盐酸小檗碱中剂量(20 mg/ml)组、盐酸小檗碱高剂量(40 mg/ml)组,每组10只,连续给药10 d后,记录各组小鼠每日尿量及10 d累计尿量,计算给药前后各组小鼠体重减轻值,检测各组小鼠血浆中TNF-α、IL-6、IL-10及IL-1β水平,取小鼠前列腺组织并计算脏器指数,苏木精-伊红染色法观察各组小鼠前列腺组织病理切片,Western blot法检测各组小鼠前列腺组织中VEGF、AKT、caspase-12蛋白表达情况。结果与模型组相比,盐酸小檗碱各剂量组小鼠累计尿量呈剂量依赖性显著增加(P<0.05),且随着给药时间的延长,盐酸小檗碱各剂量组小鼠每日尿量逐渐增加;与模型组相比,连续给药10 d后,盐酸小檗碱各剂量组小鼠的体重减轻值呈剂量依赖性显著增加(P<0.05),盐酸小檗碱各剂量组小鼠体内TNF-α、IL-6、IL-10及IL-1β等炎症因子水平、前列腺脏器指数均呈剂量依赖性显著降低(P<0.05)。病理组织学检查结果显示,与模型组相比,盐酸小檗碱各剂量组细胞形态明显改善,细胞排列整齐,腺体乳头向腔内扩张明显缩小,盐酸小檗碱中、高剂量组前列腺组织细胞形态圆润,结节样增生少见,盐酸小檗碱高剂量组小鼠的前列腺组织腺体乳头无异常突出;Western blot结果表明,与模型组相比,盐酸小檗碱各剂量组小鼠前列腺组织中VEGF及AKT表达量均呈剂量依赖性显著降低(P<0.05),caspase-12表达量呈剂量依赖性显著增加(P<0.05)。结论盐酸小檗碱能够抑制丙酸睾酮诱导的前列腺增生小鼠前列腺组织的增生,其作用机制可能与调节前列腺组织VEGF、AKT及caspase-12等蛋白的表达有关。     

萘哌地尔衍生物BWYJ抗前列腺增生的作用

目的观察萘哌地尔衍生物BWYJ对前列腺增生模型的作用。方法采用激素法建立去势大鼠和未去势小鼠前列腺增生模型,通过小鼠前列腺湿重,计算前列腺指数。光镜及透射电镜下,分别观察小鼠前列腺组织形态学及超微结构变化;TUNEL法检测BWYJ对大鼠前列腺细胞凋亡的影响。结果BWYJ5、10、20mg·kg-1组均可降低BPH小鼠前列腺湿重指数(P<0.05),光镜及电镜结果表明,BWYJ5、10、20mg·kg-1组均可抑制小鼠组织结构增生性变化,且BWYJ10、20mg·kg-1组使腺腔直径、腺体表面积变小(P<0.05)。TUNEL检测发现,大鼠前列腺凋亡细胞检出率较低,与模型组比较,BWYJ各剂量组差异无统计学意义(P>0.05)。结论BWYJ具有抗小鼠及大鼠良性前列腺增生作用。     

丙酸睾酮对去势beagle犬前列腺上皮细胞的影响

目的　探讨丙酸睾酮与犬前列腺上皮细胞生长的关系。方法　去势beagle犬经丙酸睾酮处理后 ,获取前列腺组织 ,利用放射免疫分析法 (RIA)测定前列腺组织中双氢睾酮 (DHT)含量。组织经石蜡包埋切片 ,HE染色 ,显微镜下观察前列腺的组织学变化 ,并借助显微图像分析技术测定前列腺腺腔大小及腺上皮细胞高度。免疫组织化学技术检测前列腺上皮细胞前列腺特异抗原 (PSA)及酸性磷酸酶(PAP)的表达。结果　去势犬经丙酸睾酮处理后 ,前列腺中DHT水平明显升高。光镜下前列腺腺腔增大 ,腺上皮细胞增高。图像分析结果显示前列腺腺腔面积明显增大 (P <0 .0 1) ,增大后面积分别为对照组的 4 .5～ 7倍 ,腺上皮细胞高度明显增高(P <0 .0 1) ,细胞增高幅度分别为对照组的 4～ 8倍。免疫组化结果显示丙酸睾酮处理组前列腺上皮细胞PSA表达高于对照组 (P <0 .0 5 ) ,PAP的表达也高于对照组 (P <0 .0 5 )。结论　去势犬前列腺上皮细胞生长及功能正常发挥依赖于雄激素 ,剥夺雄激素导致前列腺上皮细胞萎缩     

Ursolic acid reduces prostate size and dihydrotestosterone level in a rat model of benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is characterized by hyperplasia of prostatic stromal and epithelial cells, which can lead to lower urinary tract symptoms. The prevalence of BPH increases in an age-dependent manner. We investigated the protective effect of ursolic acid in BPH development using a testosterone-induced BPH rat model. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP), for a period of four weeks. Ursolic acid was administrated daily by oral gavage at a dose level of 5 mg/kg during the four weeks of TP injections. Animals were sacrificed on the scheduled termination, before prostates were weighed and subjected to histopathological examination. TP and dihydrotestosterone (DHT) levels in the serum and prostate were also measured. BPH-induced animals displayed an increase in prostate weight with increased testosterone and DHT levels in both the serum and prostate. However, ursolic acid treatment resulted in significant reductions in prostate weight and testosterone and DHT levels in both the serum and prostate, compared with BPH-induced animals. Histopathological examination also showed that ursolic acid treatment suppressed TP-induced prostatic hyperplasia. These findings indicate that ursolic acid may effectively inhibit the development of BPH and it may be a useful agent in BPH treatment.     

水蔓菁总黄酮对大鼠前列腺增生模型的影响

目的 探讨水蔓菁总黄酮对去势加丙酸睾酮致前列腺增生大鼠模型的作用特点.方法 大鼠摘除双侧睾丸后第8天开始,连续30d皮下注射丙酸睾酮4mg·kg-1·d-1,造大鼠前列腺增生模型,将模型大鼠分为5组,分别灌服120,60,30 mg·kg-1的水蔓菁总黄酮液、300 mg·kg-1癃闭舒胶囊混悬液和同体积生理盐水,另设...     

国产和进口十一酸睾酮雄激素活性的比较

目的 :观察国产十一酸睾酮 (TU)灌胃给药后的雄激素活性 ,并与进口TU (Andriol)比较。方法 :未成年雄性大鼠 ( 161只 ) ,去势 17d后分别灌胃给予国产TU或进口TU油溶液 5,10 ,2 0mg·kg- 1,对照组用油酸 4mL·kg- 1灌胃 ,bid× 7d ,停药 2d和 12d后各处死一半动物 ,称取前列腺和精液囊的重量。结果 :国产TU和进口TU均剂量依赖性增加去势大鼠前列腺和精液囊的重量 ,此作用在停药后可维持 10d以上 ,由六点法平行线检定得到国产TU与进口TU的相对效价 ,前列腺为1.0 7∶1;精液囊为 1∶1。结论 :国产TU的雄激素活性与进口TU相等     

The influence of small doses of ethanol on the urinary testosterone to epitestosterone ratio in men and women

Endogenous steroid use can increase urinary testosterone/epitestosterone (T/E) values. In addition, ethanol in amounts >0.5 g per kg of body weight (g/kg) can also increase T/E values. However, the effect of smaller doses of ethanol on T/E values is unknown. The influence of 0.2 and 0.4 g/kg of ethanol on baseline T/E values in 20 men and 20 women with low and high baseline T/E values was investigated and correlated with ethyl glucuronide (EtG) and ethyl sulfate (EtS) concentrations. T/E values for 7 of the women were excluded from the study because of undetectable T concentrations or for other reasons. One man and 1 woman with a high T/E baseline value had a significant increase in their T/E value after ingestion of 0.2 g/kg of ethanol. One man and 2 women with a high T/E baseline, and 1 woman with a low T/E baseline had significantly increased T/E values after ingestion of 0.4 g/kg of ethanol. There was wide variability in peak EtG concentrations and a lack of correlation between ethanol dose and EtG concentrations. Interestingly, 1 man and 2 women with increased T/E values following ethanol ingestion had EtG concentrations below the World Anti‐Doping Agency (WADA) cut‐off of 5000 ng/mL. These findings demonstrate that small amounts of ethanol can elevate T/E values, with women being more susceptible. In addition, consideration should be given to the lowering of the WADA EtG cut‐off to detect samples with elevated T/E values from ingestion of low doses of ethanol.     

当归贝母苦参丸对小鼠良性前列腺增生的抑制作用研究

目的通过研究当归贝母苦参丸（DBK）对小鼠前列腺增生（BPH）及性激素平衡的影响,为临床用药提供药理学研究依据。方法采用皮下注射丙酸睾酮制作去势小鼠前列腺增生模型,观察各组前列腺指数、性激素水平及腺细胞病理改变。结果DBK治疗14d后,与模型组相比,DBK组小鼠前列腺湿重及前列腺指数出现剂量依赖性降低（P〈0.05或P〈0.01）,明显改善前列腺组织病理结构;血清丙酸睾酮（T）、雌二醇（E2）含量明显降低（P〈0.05或P〈0.01）。结论DBK对丙酸睾酮所致小鼠BPH具有显著的拮抗作用,其作用机制在一定程度上与降低小鼠血清T、E2含量有关。     

Effect of baicalein on experimental prostatic hyperplasia in rats and mice

We determined the effect of baicalein on prostatic hyperplasia in experimental animal models. Prostatic hyperplasia was induced by testosterone propionate in mice and castrated rats and by transplantation of homologous strain fetal mice urogenital sinus in mice. With the histopathological examination, the efficacy of baicalein on prostate hyperplasia in experimental animals was evaluated by the activity of serum acid phosphatase (ACP) and the following norm of the prostate gland: the volume, wet weight, wet weight index, dry weight index, DNA contents and prostatic epithelial height and cavity diameter. Results showed that baicalein at doses of 260 and 130 mg/kg administrated intragastrically (i.g.) significantly inhibited prostatic hyperplasia in castrated rats induced by testosterone propionate compared with the negative control group (p<0.01). Baicalein at doses of 520 and 260 mg/kg (i.g.) also significantly inhibited prostatic hyperplasia in mice induced by transplantation of homologous strain fetal mouse urogenital sinus and by testosterone propionate (p<0.01). These results suggested that baicalein has an inhibitory effect on prostatic hyperplasia in experimental animals.     

Antiprostatic effect of cimetidine in rats

Administration of large doses of cimetidine for 45 days to rats decreases the weight of the prostate and seminal vesicles without affecting the testicles. The decrease in weight is due to a marked regression in the prostate of both epithelial and stromal tissue. Treatment with cimetidine also causes an increase in the plasma testosterone level without modifying the plasma values of LH and prolactin. The mechanism of action of cimetidine is discussed. In presence of high levels of testosterone, cimetidine depresses structures such as the prostate and seminal vesicles, which are sensitive to androgens, but does not depress the weight or change the histology profile of the testicles, which are also rich in androgen receptors. Perhaps cimetidine binds to androgen receptors differently in the prostate and in the testicles because of differences in receptor structure or more probably, cimetidine interacts with zinc metal ion essential to prostate growth and androgen action by lowering zinc prostatic levels and consequently depresses the prostatic weight.     

Effects of co-administration of Di(2-ethylhexyl)phthalate and testosterone on several parameters in the testis and pharmacokinetics of its mono-de-esterified metabolite

The administration of 1 g/kg di(2-ethylhexyl) phthalate (DEHP) or 5 mg/kg testosterone for 1 week did not affect the testicular and prostatic gland weights in rats. However, co-administration of DEHP and testosterone induced severe testicular atrophy accompanied by a decrease of zinc concentration in the testis and reduction of the activity of testicular specific lactate dehydrogenase isozyme. These changes were similar to the results of high dose administration of DEHP alone. Values of biological half-life and area under the concentration-time curve (AUC) of mono(2-ethylhexyl)phthalate, the main metabolite of DEHP, in testes after a single co-administration of DEHP (p.o.) and testosterone (i.p.) were higher than those after DEHP administration alone. Results suggest that the co-administration of DEHP and testosterone enhanced the adverse effects of DEHP on testes as the result of changes in pharmacokinetic values of MEHP.     

Endocrine dependence of prostatic cancer upon dihydrotestosterone and not upon testosterone

Growth of the Dunning R3327−H prostatic adenocarcinoma, implanted in the rat, is inhibited by 6−methylene progesterone. This compound is a potent inhibitor of rat prostatic 5-α-reductase and in-vivo produces marked involution of the prostate. Thus the tumor requires dihydrotestosterone and not testosterone for growth.