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。

Comparison of spontaneous and testosterone-induced benign prostatic hyperplasia in dogs

trasound detection and blood samples were collected at 24 hours before the animal were killed after the last treatment. The prostate was removed to measure the wet weight, water content, volume and to calculate the organ coefficient. Then the prostate was fixed in 10% formalin solution, embedded in paraffin, sectioned at 4 μm, and stained with hematoxylin and eosin. Slides were observed under microscope and analyzed the height of prostatic epithelium （HPE） and acinar luminal area（ALA） with a micro-image analysis system （MIVNT）. T level, dihydrotestosterone （DHT） level, prostate specific antigen（PSA） level and prostate acid phosphatase （PAP） level in serum and prostate were assayed according to the instruction of magimuzyme kits and ELISA kits. Results ①After 4 weeks treatment, the mean body weight of dogs in the three groups were smoothly increased. ②The ultrasound showed that the prostate volumes of animals in the T group and old dog group were significantly larger than that of the normal control group （ P 〈 0.01 ）. ③The real prostate volumes of T group and old dog group were significantly larger than that of control （P 〈 0.05 ） , and the prostate volume of the old dog group was larger than that of the T group. Compared with the control, the prostate wet weight and organ coefficient of T group and old dog group were significantly increased （ P 〈 0. 05 ）, and both indexes of the old dog group were greater than that of the T group. ④Aceording to the data of histopathology, in the T group, the hyperplastic prostate showed more hyperplastic glands, especially was prostatic epithelium proliferation, while in the old dog group, the hyperplastic prostate mostly contributes to prostatic mesenchyme proliferation. Further MIVNT results showed that, compared with the control, the HPE was significantly increased （P 〈 0. 01 ） and the ALA was significantly enlarged in the T group （P 〈 O. 01 ） , while in old dog group, the HPE was also significantly increased （ P 〈 0.01 ） and the ALA was significantly enlarged （ P 〈 0. 05 ） , but its HPE was lower than that of the T group. ⑤Compared with the control, in T group, the T, DHT and PAP levels in serum were slightly increased, and T （ P 〈 0. 05 ）, DHT （ P 〈 O. 01 ）, PAP （ P 〈 0.05 ） and PSA levels in prostate were significantly increased. In the old dog group, the T, DHT and PAP levels in serum were slightly increased, the T level in prostate was slightly increased, and the DHT, PAP and PSA levels in prostate were slightly decreased. Conclusion Both spontaneous and testosterone-induced BPH model in dogs can be used to evaluate BPH drugs, but there are some differences between these two groups.