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谢金东,杨燕燕,周建华,李志雄,林玮,俞春英,刘德强,王训立.2018.猕猴前列腺增生动物模型的建立.动物学杂志,53(6):978-985.
猕猴前列腺增生动物模型的建立
Establishment of Benign Prostate Hyperplasia Model of Rhesus Monkey
投稿时间:2018-01-11  修订日期:2018-10-16
DOI:10.13859/j.cjz.201806015
中文关键词:  猕猴  前列腺增生  双氢睾酮  丙酸睾酮  B型超声
英文关键词:Rhesus monkeys, Macaca mulatta  Benign prostate hyperplasia  Testosterone propionate  Dihydrotestosterone  Type-B ultrasonic
基金项目:福建省科技计划项目(引导性)(No. 2016Y0051)
作者单位E-mail
谢金东 福建中医药大学实验动物中心 584233760@qq.com 
杨燕燕 福建中医药大学实验动物中心 yanfjtcm@163.com 
周建华 福建中医药大学实验动物中心 zjh001866@sina.com 
李志雄 福建省计划生育科学技术研究所 lizx5678@126.com 
林玮 福建中医药大学实验动物中心 34945011@qq.com 
俞春英 福建中医药大学实验动物中心 yuchunying_2009@126.com 
刘德强 福建中医药大学实验动物中心 120087762@qq.com 
王训立 福建中医药大学实验动物中心 wangxunli@139.com 
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中文摘要:
      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。
英文摘要:
      Rhesus Monkeys (Macaca mulatta) were used to provide a better benign prostate hyperplasia (BPH) model, and to explore the optimal conditions. A total of 12 male rhesus monkeys were divided into treatment and control groups at random and were administrated testosterone propionate (TP) through hypodermic injection for eight weeks after castration. Three treatment groups were given 0.8, 2.5, 7.5 mg/(kg?d) TP respectively, and the control group was given the same volume of vehicle. The prostate volumes of rhesus monkeys were measured with ultrasonic diagnosis instrument before castration, at eight weeks after castration, at four weeks and eight weeks after being given TP. Then, the serum of monkeys at all these experimental stages were separated and collected. Eight weeks later of being given TP, the rhesus monkeys were killed and the prostates were prepared. After the wet weight and volume of prostate were measured, paraffine section of BPH was stained by the H.E methods. Pictures were taken by digital camera under microscope, and all the pictures were analyzed by computer for epithelial cell height and acinar luminal area of prostate with micro image analysis soft ware. And then, the dihydrotestosterone (DHT) level of serum and prostate were detected with ELISA kit. The comparison of difference between groups was analyzed with independent-samples T test method using SPSS 13.0. The ultrasonic results showed that the prostate volumes of all the rhesus monkeys at eight weeks after castration were smaller than before castration (P < 0.05). After having been administrated TP for four weeks and for eight weeks, the prostate volumes of all treatment groups were larger than the control group (P < 0.05), and the best was mid-dose group (P < 0.01). But with TP administration for four weeks and for eight weeks, there were no significant differences between treatment groups (P > 0.05) (Table 1). The wet weights and volumes of the prostate of all treatment groups were higher than those of the control group (P < 0.05), and the maximum was mid-dose group (Table 3). The results of micro image analysis showed that the acinar luminal area and the epithelial cell height of prostate of all treatment groups were increased than the control group (P < 0.01) (Table 4, Fig. 2). The DHT level of serum (P < 0.01) and prostate (P < 0.05) of the rhesus monkeys of all treatment groups were increased than the control group, and the maximum was mid-dose group. But with TP administration for four weeks and for eight weeks, there were no significant differences between treatment groups (P > 0.05) (Table 2 and 4 ). It is practicable to establish BPH model in rhesus monkeys with TP administration. It is initially determined that the suitable conditions for the TP dose of 2.5 mg/(kg?d), and for the delivery time of 4 weeks.
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