猕猴前列腺增生动物模型的建立

利用猕猴（Macaca mulatta）建立前列腺增生动物模型,并探讨丙酸睾酮（TP）诱导猕猴前列腺增生模型的最佳剂量及给药时间。雄性猕猴12只,随机分为3个剂量的实验组和对照组共4组,每组3只。去势8周后,皮下注射给药。实验组按低、中、高剂量分别给予丙酸睾酮（TP）0.8、2.5、7.5 mg/(kg?d),对照组给予等体积溶剂,连续8周。B型超声探测去势前、去势后8周及TP干预4周、8周时猕猴前列腺体积,并采集分离各个实验阶段的血清备用。给药8周后处死动物,取前列腺,称量湿重,测量体积,计算前列腺重量指数及体积指数,H.E染色切片观察前列腺增生情况,并进一步测量腺腔面积及腺上皮细胞高度。同时,采用ELISA方法测定血清及前列腺组织中二氢睾酮（DHT）水平。B型超声结果显示,去势8周时,各组猕猴前列腺体积均明显小于去势前（P < 0.05）。TP干预4周及8周时,各剂量组猕猴前列腺体积均显著大于对照组（P < 0.05）,且在干预4周TP中剂量组达到最佳效果（P < 0.01）。而TP干预4周与8周相比,各组间并无显著性差异（P > 0.05）。解剖结果显示,各实验组猕猴前列腺湿重、体积及脏器指数均明显大于对照组（P < 0.05）,且在中剂量组达到最大值。而显微图像分析结果显示,实验组猕猴前列腺上皮细胞增生,与对照组比较,各剂量组猕猴前列腺腺腔面积明显增加（P < 0.01）,腺上皮细胞高度明显增高（P < 0.01）。二氢睾酮（DHT）水平检测结果显示,与对照组相比,药物干预后各实验组猕猴血清中DHT含量明显增高（P < 0.01）,且在中剂量组达到最大值。TP干预4周与8周相比,各组间并无显著性差异（P > 0.05）。同时,各实验组前列腺组织中DHT含量相较于对照组也明显增高,但剂量-效应关系不显著,中剂量组优于高、低剂量组。TP药物干预去势猕猴可成功建立猕猴前列腺增生模型,初步判定较为适宜的造模条件为丙酸睾酮给药剂量2.5 mg/(kg?d),给药时间4周。     

桂枝茯苓胶囊对小鼠尿生殖窦植入性前列腺增生的影响

观察桂枝茯苓胶囊对小鼠前列腺增生病理模型的影响。方法 :用小鼠尿生殖窦植入小鼠前列腺 ,建立前列腺增生病理模型 ,用桂枝茯苓胶囊连续灌胃给药 30天 ,测定前列腺重量和体积并进行病理学检查。结果 :与模型组比较 ,桂枝茯苓胶囊可明显减轻小鼠前列腺重量 ,减小小鼠前列腺体积 (P<0 .0 5 ;P<0 .0 1)。病理结果显示桂枝茯苓胶囊组小鼠前列腺增生轻于模型组。桂枝茯苓胶囊对小鼠前列腺增生具有抑制作用     

自发性及睾酮诱导犬前列腺增生模型的比较

目的比较自发性及雄激素诱导犬前列腺增生模型的特点,为更好地评价治疗前列腺增生药物奠定方法学基础。方法成年雄性Beagle犬12只,随机分成2组,B超探测符合要求的老年Beagle犬6只,依次设为对照组、睾酮组和老年犬组（即自发性前列腺增生组）。睾酮组动物去势后,经肌肉注射（im）2.5 mg/kg的睾酮,对照组动物给予等体积溶媒,老年犬组动物不给药,连续4周。每周称重一次,最后一次给药24 h后,B超探测前列腺体积,采血,取血清备用。麻醉处死动物,取前列腺,称干湿重,测量前列腺体积,计算前列腺脏器系数,组织切片,HE染色后镜下观察前列腺病理组织学变化,并进一步利用显微图像软件测量前列腺上皮高度及腺腔面积。利用磁酶免和ELISA方法检测血清及前列腺组织中睾酮（T）、双氢睾酮（DHT）、前列腺特异抗原（PSA）和前列腺酸性磷酸酶（PAP）水平。结果①给药后,各组动物体重增长总体呈平稳趋势。②B超结果显示,去势Beagle犬给予睾酮4周,前列腺体积大于对照组（P〈0.01）,老年犬前列腺体积大于成年犬（P〈0.01）。③解剖结果显示,睾酮组和老年犬组实际前列腺体积均明显大于对照组（P〈0.05）,且老年犬前列腺体积大于睾酮组;睾酮组和老年犬组前列腺湿量和脏器系数均大于对照组（P〈0.05）,且老年犬前列腺湿重和脏器系数均大于睾酮组。④病理形态分析显示,睾酮组犬前列腺镜下主要表现为腺体增生,尤其是腺上皮增生,而老年犬则更多表现为间质增生。显微图像分析结果显示,与正常对照组相比,睾酮组前列腺上皮高度增加（P〈0.01）,腺腔面积增大（P〈0.01）;老年Bea-gle犬同样表现为前列腺上皮高度增加（P〈0.01）,腺腔面积增大（P〈0.05）,但上皮高度要低于睾酮组。⑤激素检测结果显示,与对照组相比,睾酮组血清中T、DHT和PAP水平略升高,前列腺组织中T（P〈0.05）、DHT（P〈0.01）、PAP（P〈0.05）和PSA水平升高明显;老年犬血清中T、DHT和PAP水平略升高,前列腺组织中T升高,但DHT、PAP和PSA水平均较正常组为低。结论自发性和睾酮诱导的犬前列腺增生模型均可用于前列腺增生药物评价,但模型间存在一定的差异性。     

雄性大鼠颌下腺雄激素受体表达及镉和丙酸睾酮对其的影响

目的探测雄性大鼠颌下腺内雄激素受体(AR)表达及细胞分布特征,了解氯化镉和丙酸睾酮对AR表达的影响。方法35只雄性Wistar大鼠分为3组:对照(C)组、镉(Cd)组和镉加丙酸睾酮(Cd T)组。利用免疫组化SABC法和图像分析系统作AR表达检测及平均光密度(AOD)值定量分析。结果AR在浆液性腺泡(AC)、颗粒曲管(GCT)、纹状管(SD)和排泄管等细胞内均有不同程度的表达,定位以细胞质为主。其中GCT细胞内AR的AOD值最高,SD次之,AC细胞最低。Cd处理24h后,三种细胞内AR的AOD值均见下降,7d时达最低水平,此后有所增加,但到30d时仍低于对照组(P<0.05)。Cd T处理后,GCT细胞内AR的AOD值明显增加。与3、7、15d时Cd组相比,差别均有显著性。AC和SD细胞内AR的AOD值虽高于相应时间点的Cd组,但两者比较仅在7d时差别有显著性。结论雄性大鼠颌下腺内广泛存在AR,镉可致颌下腺GCT、AC、SD细胞AR表达减少,补充雄激素可明显增加GCT细胞AR表达,但对AC和SD细胞AR表达的影响较小。     

自噬抑制剂氯喹对急性酒精诱导小鼠肝损伤的影响

目的：探讨自噬抑制剂氯喹（CQ）对急性酒精诱导肝损伤的影响及其作用机制。方法：将雄性C57BL/6小鼠随机分为3组：正常对照组、酒精组、氯喹干预组（n=7）,其中酒精组按4.5 g/kg剂量给予33%（V/V）酒精灌胃。HE和油红O染色检测各组小鼠肝组织脂滴变化;检测肝组织甘油三酯（TG）含量变化;检测血清谷草转氨酶（AST）和谷丙转氨酶（ALT）活性;免疫荧光法检测微管相关蛋白轻链3（LC3）蛋白变化;Western blot法检测LC3蛋白和核蛋白P65表达的变化;ELISA法检测促炎因子TNF-α、IL-6的变化。结果：与对照组比较,酒精组脂滴形成、TG含量、血清AST和ALT活性明显增高。与对照组比较,酒精组LC3-Ⅱ蛋白表达明显增加;与酒精组比较,氯喹干预组使酒精诱导的LC3-Ⅱ蛋白表达增强进一步加剧,使酒精诱导的TG含量、血清AST和ALT活性进一步增高,同时增加了酒精诱导的p65入核及TNFα、IL-6释放。结论：急性酒精能引起小鼠肝脏脂肪变化及炎症,而自噬抑制剂氯喹抑制自噬进程,加剧酒精诱导的肝损伤,说明自噬在酒精诱导肝损伤中可能具有保护效应。     

通过酒精饲养小鼠建立小鼠酒精模型

研究通过酒精饲养小鼠建立小鼠酒精成瘾模型的方法。使用6周龄SPF级Balb/c雄性小鼠15只,随机分为3组(n=5),即灌胃和酒水喂养组(A)、灌胃组和水喂养组(B)、对照组(C)。3组固体饲料正常给予,A、B两组每日灌胃11%酒水200μL,A组酒水溶液自由摄取并作为唯一饮水来源,B组水自由摄取,C组不做处理。饲养8周后进行24 h酒精戒断,并进行矿场实验,强迫游泳实验。处死小鼠取肝脏、肾脏和结肠制作石蜡切片并观察。造模过程中3组小鼠进食、饮水、体重、内脏重量出现了不同程度的变化。行为学结果显示,矿场实验中A、B两组小鼠戒断酒精后相对对照组小鼠焦虑水平明显升高;强迫游泳实验中,A、B两组相对C组绝对不动时间显著加长,表现出精神抑郁。显微镜观察小鼠内脏石蜡切片,A组小鼠肝脏切片明显出现肝细胞排列紊乱,肾脏中肾小球上皮细胞轻度萎缩,空泡变性,肾小管无明显病变,结肠石蜡切片肠绒毛出现破损,肠绒毛顶端完整性降低。B组肝、肾、结肠石蜡切片与对照组相比无明显变化。     

血清前列腺特异性抗原与前列腺增生的相关性研究

目的:探讨前列腺增生患者年龄,前列腺体积以及BMI与血清前列腺特异性抗原(PSA)之间的关系。方法:对224例前列腺增生患者的年龄,前列腺体积以BMI与PSA的相关性进行Spearman相关性分析。结果:224例前列腺增生患者有25%的患者PSA水平高于正常,并且年龄,前列腺体积与血清PSA存在明显的正相关:(r=0.672.P<0.01,r=0.785.P<0.01),而血清PSA与BMI指数存在明显的负相关:(r=-0.873,P<0.01)。结论:前列腺增生患者的血清PSA值随患者年龄增长和体积增大而增加,对于PSA轻度升高的前列腺增生患者,要考率到体重因素对结果的影响。     

血清前列腺特异性抗原与前列腺增生的相关性研究

目的：探讨前列腺增生患者年龄,前列腺体积以及BMI与血清前列腺特异性抗原（PSA）之间的关系。方法：对224例前列腺增生患者的年龄,前列腺体积以BMI与PSA的相关性进行Spearman相关性分析。结果：224例前列腺增生患者有25％的患者PSA水平高于正常,并且年龄,前列腺体积与血清PSA存在明显的正相关：（r=0．672．P〈0．01,r=0．785．P〈0．01）,而血清PSA与BMI指数存在明显的负相关：（r=-0．873,P〈0．01）。结论：前列腺增生患者的血清PSA值随患者年龄增长和体积增大而增加,对于PSA轻度升高的前列腺增生患者,要考率到体重因素对结果的影响。     

Dual‐wavelength‐assisted thermal hemostasis for treatment of benign prostate hyperplasia

Laser treatment on a large size of prostate gland often encounters significant bleeding that can prolong the entire procedure and cause urinary complications. The current study investigates the feasibility of dual‐wavelength (532 and 980 nm) application to achieve rapid hemostasis for 532‐nm laser prostatectomy. Porcine kidney and bleeding phantom models were tested to quantify the degree of the irreversible tissue coagulation and to estimate the time for the complete hemostasis, respectively. The ex vivo kidney testing verifies that the dual‐wavelength created up to 40% deeper and 25% wider coagulation regions than a single wavelength does. The bleeding phantom testing demonstrates that due to the enhanced thermal effects, the simultaneous irradiation yields the complete photocoagulation (~11 seconds) whereas 532 or 980 nm hardly stops bleeders. Numerical simulations validate that the combined optical‐thermal characteristics of both the wavelengths account for the augmented thermal coagulation. The dual‐wavelength‐assisted coagulation can be a feasible treatment to entail the rapid hemostasis and to facilitate the laser prostatectomy in an effective manner.      

A lectin histochemistry comparative study in human normal prostate, benign prostatic hyperplasia, and prostatic carcinoma

The partial oligosaccharide sequences of glycoconjugates and the nature of their glycosidic linkages were investigated in normal human prostate, benign prostatic hyperplasia (BPH) and prostatic carcinoma by means of lectin histochemistry, using light microscopy and Western blot analysis. The labeling pattern of BPH differed from that of normal prostate in having more intense staining with DSA, HPA, UEA-I and AAA, and in showing lesser staining with WGA and SBA. Prostatic carcinoma differed from normal prostates in displaying the more intense labeling with PNA, DSA, SBA, DBA, UEA-I and AAA, and in having lesser labeling with WGA. The main differences in labeling pattern between prostatic carcinoma and BPH were that the latter specimens showed more marked staining with PNA, DSA, DBA, SBA, UEA-I and AAA, and lesser staining with WGA and HPA. The staining patterns of SNA, MAA, ConA, LCA and GNA were similar in all three groups of specimens. For most of the lectins studied, including those showing a similar immunohistochemical staining in the three groups of specimens studied, the Western blot analysis showed differences in the banding pattern among normal, hyperplastic, and carcinomatous prostates. Present results suggest that the glycosylation of proteins was modified in both BPH and prostatic carcinoma. In BPH a strong expression of N-acetylgalactosamine residues occurred, while in prostatic carcinoma an increase of sialic aci, galactose and fucose residues was observed. No changes in mannose residues were detected.     

Protocatechuic acid ameliorates testosterone‐induced benign prostatic hyperplasia through the regulation of inflammation and oxidative stress in castrated rats

Protocatechuic acid (PA) is a polyphenol—recognized for its efficacy as an antioxidant—possesses anticancer, anti‐inflammatory, antioxidant properties. The efficacy of PA in the management of benign prostatic hyperplasia (BPH) has not been investigated. Forty‐two castrated rats (n = 7) were treated as follows: control (corn oil), BPH only received testosterone propionate (TP) (TP 3 mg/kg intraperitoneally), BPH + PA (TP 3 mg/kg + PA 40 mg/kg), BPH + finasteride (Fin) (TP 3 mg/kg + Fin 10 mg/kg), PA only (40 mg/kg: by gavage), and Fin only (10 mg/kg: by gavage) for 4 weeks. In BPH rats, there were significant (P < .05) increases in prostatic (250%) and organosomatic (280%) weights compared with controls. Cotreatment decreased prostatic weights by 19% (PA) and 21% (Fin). Markers of inflammation: myeloperoxidase activities increased in serum (148%) and prostate (70%), as well as nitric oxide levels serum (92%) and prostatic (95%). Proinflammatory cytokines interleukin‐1β and tumor necrosis factor‐α increased by 3.6‐ and 2.8‐fold. Furthermore, prostatic malondialdehyde, superoxide dismutase, and serum total acid phosphatase increased by 97%, 25%, and 48%, respectively. Histology revealed poor architecture and severe proliferation of the prostate in BPH rats. Inflammation and oxidative stress markers, as well as the histological alteration in BPH rats, was attenuated (P < .05) upon cotreatment with PA and comparable with Fin cotreatment. These results suggest that PA mitigates oxido‐inflammatory responses and restored prostatic cytoarchitecture to levels comparable with control in rats induced with BPH.     

Effects of Panax ginseng on the nerve growth factor expression in testosterone induced benign prostatic hyperplasia

The prostatic hyperplasia in benign prostatic hyperplasia (BPH) leads to obstructive micturition symptoms. Previous studies showed that pontine micturition center (PMC), ventrolateral periaqueductal gray (vlPAG), and medial preopticnucleus (MPA) regions in the brain have been known to regulate the urinary bladder function. The present study shows the influences of Panax ginseng on nerve growth factor (NGF) expressions in PMC, vlPAG, and MPA regions in the brain. Wistar rats were used for the present study. The rats split into four groups; 4 groups (n = 6) in control group, BPH-induced group, BPH-induced and P. ginseng-treated group, and BPH-induced and finasteride-treated group. BPH in rats was induced by testosterone and the animals were evaluated for NGF expression in PMC, vlPAG, and MPA regions in the brain. The NGF expression was identified using immunohistochemistry (IHC). The NGF expression by IHC showed spots with dark brown color. In our results, NGF expressions in PMC, vlPAG, and MPA regions in the brainstem of the BPH-induced group showed increase than the control animal. These increased NGF expressions in three regions were decreased using treatment with P. ginseng (200 mg/kg). These results suggest that P. ginseng has therapeutic effects on the symptoms of BPH and is associated with the regulation of NGF expression in the brain. In conclusion, the administration of P. ginseng helps nerve growth factor activation.     

Use of Tregs as a cell‐based therapy via CD39 for benign prostate hyperplasia with inflammation

Benign prostatic hyperplasia (BPH) occurs most commonly among older men, often accompanied by chronic tissue inflammation. Although its aetiology remains unclear, autoimmune dysregulation may contribute to BPH. Regulatory T cells (Tregs) prevent autoimmune responses and maintain immune homeostasis. In this study, we aimed to investigate Tregs frequency, phenotype, and function in BPH patients and to evaluate adoptive transfer Tregs for immunotherapy in mice with BPH via CD39. Prostate specimens and peripheral blood from BPH patients were used to investigate Treg subsets, phenotype and Treg‐associated cytokine production. Sorted CD39^+/? Tregs from healthy mice were adoptively transferred into mice before or after testosterone propionate administration. The Tregs percentage in peripheral blood from BPH patients was attenuated, exhibiting low Foxp3 and CD39 expression with low levels of serum IL‐10, IL‐35 and TGF‐β. Immunohistochemistry revealed Foxp3+ cells were significantly diminished in BPH prostate with severe inflammatory. Although the Tregs subset was comprised of more effector/memory Tregs, CD39 was still down‐regulated on effector/memory Tregs in BPH patients. Before or after testosterone propionate administration, no alterations of BPH symptoms were observed due to CD39‐ Tregs in mice, however, CD39⁺Tregs existed more potency than Tregs to regulate prostatic hyperplasia and inhibit inflammation by decreasing IL‐1β and PSA secretion, and increasing IL‐10 and TGF‐β secretion. Furthermore, adoptive transfer with functional Tregs not only improved prostate hyperplasia but also regulated muscle cell proliferation in bladder. Adoptive transfer with Tregs may provide a novel method for the prevention and treatment of BPH clinically.     

Dose–response effect of Red Maca (Lepidium meyenii) on benign prostatic hyperplasia induced by testosterone enanthate

The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required.     

Effect of testosterone on long-term organ cultures of canine prostate

Summary Organ cultures of rodent and human prostate glands have shown marked differences in their morphological response to testosterone. In this study, explants from 19 canine prostate glands were cultivated for a minimum of 9 days in Trowell’s T-8 medium. Groups of explants were exposed to media containing from 0.05 to 100 μm testosterone. While the higher testosterone levels (50 and 100 μm) markedly decreased explant viability, explants cultivated at lower levels (0.05 to 5 μm) appeared similar to control explants in testosterone-free Trowell’s T-8 medium. Atmospheric mixtures containing either 95% or 50% oxygen were equally effective. Shortly after the cultures were initiated, large amounts of secretory product were liberated into the lumen. After 9 or more days in vitro, glandular epithelium appeared cuboidal and never revealed the acid phosphatase-rich secretory granules seen in the preculture control. However, the epithelium exhibited an increase in alkaline phosphatase and lipid content following cultivation. This project was supported by contract N01-CP-33331, Carcinogenesis Program, Division of Cancer Cause and Prevention, National Cancer Institute, Bethesda, Maryland.     

Selenium in combination with a tomato lipid extract as a therapy for benign prostatic hyperplasia and its alterations in rats with induced BPH

Benign prostatic hyperplasia (BPH) is the most common adenoma in old men. Tomatoes are a rich source of bioactive compounds that, as well as selenium (Se), possess antioxidant and antiproliferative activity. The aim was to evaluate the therapeutic effect of Se in combination with a tomato extract in aged rats with BPH. Aged male Wistar rats were divided in the following groups (n = 10 rats/group): Control (C), BPH, BPH + Finasteride (BPH + F), BPH + Tomato Lipidic Extract (BPH + E), BPH + Selenium (BPH + S) and BPH plus E plus S (BPH + E + S). After 4 weeks of treatment, prostate weight, diuresis, antioxidants enzymes, prooxidants and inflammatory markers, growth factors and androgens were determined. BPH + E + S reduced prostate weight by 59.29% and inhibited growth by 99.35% compared to BPH + F which only decreased weight and inhibited growth by 15.31% and 57.54%, respectively. Prooxidant markers were higher with BPH + F (49.4% higher vs. BPH), but BPH + E + S decreased these markers (94.27% vs. BPH) and increased antioxidant activity. Finally, diuresis was higher with the BPH + E + S combination and markers of inflammation and growth factors were significantly lower with respect to BPH + F. Our findings provide a beneficial and protective therapeutic option of E + S directed against androgens, oxidative stress and inflammation that regulates cell proliferation in the prostate gland.     

Selenium level in benign and cancerous prostate

The dietary microelement selenium (Se) has been proposed as a potential chemopreventive agent for prostate cancer. This element is present in various amounts in all tissues. Little information is available on Se level in patients with prostate gland disorders. The levels of Se in prostatic gland of patients with prostate cancer, benign prostate hyperplasia, and healthy controls were examined. The Se level for benign prostate hyperplasia (156±30.6 ng/g) was the same as in the control group (157±26.0 ng/g), but in the gland of prostate cancer patients (182±34.1 ng/g wet weight), the Se level was significantly (p<0.01) higher than in both healthy controls and benign prostate hyperplasia. Thus, the Se level in human healthy controls is lower than in kidney and liver but higher compared with other tissues.