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良性前列腺增生合并迟发性性腺功能减退大鼠模型的构建
秦盛斐1△,徐剑1△,翦晓明2,陈光华1,肖广安1,何妙侠3,LAIH.Henry4,周铁1*
0
(1. 第二军医大学长海医院泌尿外科, 上海 200433;
2. 上海市杨浦区市东医院泌尿外科, 上海 200438;
3. 第二军医大学长海医院病理科, 上海 200433;
4. Division of Urologic Surgery, Washington University School of Medicine, St Louis, MO63110, USA
共同第一作者
*通信作者)
摘要:
目的 探讨良性前列腺增生(BPH)合并迟发性性腺功能减退症(LOH)动物模型的建立方法,并分析其特点。方法 选取80只SD大鼠,随机分为对照组、BPH合并LOH组、BPH组、LOH组,每组均为20只。BPH合并LOH组给予环磷酰胺[20 mg/(kg·d)]腹腔内连续注射5 d,而后给予丙酸睾酮[50 mg/(kg·d)]腹腔内连续注射28 d;BPH组以同等体积生理盐水代替环磷酰胺,LOH组以同等体积橄榄油代替丙酸睾酮,对照组以同等体积生理盐水代替环磷酰胺、同等体积橄榄油代替丙酸睾酮,给药方法同BPH合并LOH组。停药2 d后,进行悬尾实验、负重游泳实验及交配实验,并通过断尾法取血以检测血清睾酮含量。完成全部操作后,通过颈椎脱臼法处死全部实验动物,解剖观察前列腺、称量并行组织病理学检查。结果 LOH组、BPH合并LOH组、对照组、BPH组大鼠平均前列腺指数分别为1.58±0.13、2.93±0.19、2.33±0.13、3.23±0.11,血清睾酮含量分别为(4.91±1.06)、(9.52±1.02)、(12.59±0.70)、(19.69±0.56) ng/mL,悬尾挣扎次数分别为(97.40±15.86)、(120.40±14.06)、(223.83±16.51)、(235.29±18.77)次,各组间差异均有统计学意义(P<0.05,P<0.01);LOH组、BPH合并LOH组、对照组、BPH组大鼠平均负重游泳时间分别为(74.27±9.29)、(167.47±23.35)、(302.33±30.10)、(261.59±35.13) s,嗅阴次数分别为(1.53±0.52)、(3.07±0.88)、(9.17±1.30)、(9.59±1.12)次,除对照组和BPH组差异无统计学意义外,其余各组间差异均有统计学意义(P<0.01);LOH组、BPH合并LOH组、对照组、BPH组大鼠平均骑跨次数分别为(0.33±0.49)、(0.47±0.52)、(2.11±0.47)、(2.29±0.47)次,除对照组与BPH组、BPH合并LOH组与LOH组差异无统计学意义外,其余各组间差异均有统计学意义(P<0.01)。结论 通过腹腔注射环磷酰胺及丙酸睾酮可获得BPH合并LOH大鼠模型。
关键词:  前列腺增生  迟发性性腺功能减退症  动物模型  环磷酰胺  丙酸睾酮
DOI:10.16781/j.0258-879x.2017.07.0865
投稿时间:2016-12-03修订日期:2017-01-27
基金项目:第二军医大学长海医院"1255"学科建设计划(CH125520302).
Establishment of a rat model of benign prostatic hyperplasia complicated with late-onset hypogonadism
QIN Sheng-fei1△,XU Jian1△,JIAN Xiao-ming2,CHEN Guang-hua1,XIAO Guang-an1,HE Miao-xia3,LAI H. Henry4,ZHOU Tie1*
(1. Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
2. Department of Urology, Shidong Hospital of Yangpu District, Shanghai 200438, China;
3. Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
4. Division of Urologic Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
Co-first authors
*Corresponding author)
Abstract:
Objective To establish and assess a rat model of benign prostatic hyperplasia (BPH) complicated with late-onset hypogonadism (LOH). Methods A total of 80 SD rats were randomly divided into 4 groups:control group, BPH complicated with LOH (model) group, BPH group and LOH group, with 20 rats in each group. In the model group, intraperitoneal injection of cyclophosphamide (20 mg/[kg·d]) was continuously administered for 5 days, followed by continuous intraperitoneal injection of testosterone propionate (50 mg/[kg·d]) for 28 days; the rats in the BPH group were treated the same as that in the model group, except with the same volume normal saline instead of cyclophosphamide; in the LOH group with same volume lucca oil instead of testosterone propionate; and in the control group, the rats were treated with same volume normal saline instead of cyclophosphamide and lucca oil instead of testosterone propionate. Two days after drug withdraw, serum testosterone was detected and weight loading swimming test, tail suspension test and sexual behavior test were performed. Then prostate weight and pathology were determined after the rats were sacrificed by cervical dislocation. Results The mean prostate indexes of rats in the LOH, model, control and BPH groups were 1.58±0.13, 2.93±0.19, 2.33±0.13 and 3.23±0.11, respectively; serum testosterone levels were (4.91±1.06), (9.52±1.02), (12.59±0.70) and (19.69±0.56) ng/mL, respectively; the tail suspension struggling times were 97.40±15.86, 120.40±14.06, 223.83±16.51, and 235.29±18.77, respectively; the weight loading swimming times were (74.27±9.29), (167.47±23.35), (302.33±30.10) and (261.59±35.13) s, respectively; the times of olfactory sensation were 1.53±0.52, 3.07±0.88, 9.17±1.30 and 9.59±1.12, respectively; the mean ride across times were 0.33±0.49, 0.47±0.52, 2.11±0.47 and 2.29±0.47, respectively. Statistical analyses showed that there were significant differences among the four groups in mean prostate index, serum testosterone level and tail suspension struggling time (P<0.05, P<0.01), in weight loading swimming time and time of olfactory sensation (P<0.01) except between control group and BPH group, and in mean ride across time (P<0.01) except between control group and BPH group, and model group and LOH group. Conclusion A BPH complicated with LOH rat model was successfully established with intraperitoneal injection of cyclophosphamide and testosterone propionate.
Key words:  prostatic hyperplasia  late-onset hypogonadism  animal models  cyclophosphamide  testosterone propionate