犬输精管结扎术后前列腺细胞凋亡与Bcl-2 Bax基因表达

Cell apoptosis and Bci-2 Bax gene expressions of prostate after vasectomy in pooches

目的观察输精管及其静脉结扎（以下简称“结扎”）对老年犬前列腺增生模型组织学、细胞凋亡及Bcl-2、Bax基因表达的影响。方法12只雄性杂交5～6岁犬用添加甲基睾丸素的犬饲料喂养2年制成前列腺增生动物模型,造模成功后,随机分为结扎组（施行输精管及其静脉结扎术）和假手术组,继续饲养2年后处死犬。取前列腺测量体积并称重,标本分别行HE染色、免疫组化染色检测增殖细胞核抗原（PCNA）及凋亡抑制基因（Bcl-2）、促凋亡基因（Bax）蛋白表达。结果结扎后结扎组增生的前列腺体积变小、重量减轻,腺体出现萎缩性变,而假手术组前列腺仍呈增生性改变（P〈0.01）;结扎组前列腺腺上皮面积比（0.16±0.05）和腺上皮平均高度[（55.67±8.34）μm]均呈下降趋势,而假手术组上述检测指标分别为（0.24±0.07）、[（108.81±15.26）μm],均高于结扎组（P〈0.01）,间质面积比结扎组（0.65±0.12）高于假手术组（0.46±0.09）（P〈0.05）.结扎后前列腺萎缩主要以腺体和腺上皮为主;免疫组化结果显示,PCNA在结扎组前列腺腺上皮细胞核中表达较弱,在假手术组中表达较强;Bcl-2基因蛋白在结扎组前列腺上皮胞浆中表达较弱,在假手术组中表达较强;Bax基因蛋白在结扎组前列腺上皮胞浆中表达较强,在假手术组中表达较弱;结扎组PCNA和Bcl-2阳性信号的面密度值下调[分别为（0.29±0.05）、（0.18±0.07）],低于假手术组[分别为（0.67±0.12）、（0.27±0.1）],而Bax阳性信号面密度值（0.29±0.07）上调,高于假手术组（0.12±0.02）,两组差异有统计学意义（P〈0.01）;结扎组增殖指数（0.12±0.01）和假手术组（0.24±0.13）相比,差异有统计学意义（P〈0.01）。结论前列腺细胞凋亡与Bcl-2、Bax基因调控密切相关,输精管结扎术后局部激素的阻断使老年犬前列腺组织细胞出现萎缩、细胞增殖下降、细胞凋亡增加,通过改变腺体细胞中Bcl-2与Bax基因的表达而实现对增殖与凋亡的调控是输精管结扎后发生凋亡的可能机制之一。

Objective To investigate the prostate cell apoptosis and Bcl-2, Bax gene expressions of pooch＇s benign prostatic hyperplasia （BPH） after vasectomy and vein ligation. Methods The model of BPH was established in 12 male pooches by feeding the methyhestosterone-containing food. Two years later, the pooches were divided into treatment group and sham-operated group randomly. Each group bad 6 pooches. The pooches in treatment group were performed vasectomy and deferent veins ligation on both sides, while pooches in sham-operated group were only performed dissection relieving ductus deferens. The 12 pooches continued to feed after operation, and were killed another two years later. The volume and weight of the prostates were calculated, and changes of histology and pathology of the prostate were observed. The prostates were detected for apoptosis by proliferating cell nuclear antigen （PCNA）, Bcl-2 and Bax by immunohistochemistry. Results The weights and volumes of treatment group were decreased and the prostate gland tissues bad obviously atrophic changes, while hyperplasia changes were observed in sham-operated group. Significant differences were found between the two groups （all P〈0.01）. The ratio of the area of glands （0.16 ±0.05）, average height of epithelium [（55.67 ±8.34）μm ] in treatment group were lower than those in the sham-operated group [（0. 24±0. 07）μm,（108. 81±15.26）μm] （P（0.01）, while the ratio of the area of stroma in treatment group was higher than that in the sham-operated group [（0. 65±0.12） vs. （0.46 ±0.09） （ P 〈 0.05 ）], the atrophy occurred predominantly in prostate glands and epithelia. PCNA and Bcl-2 positive expressions and the detection of area density of positive signal（Sa）[（0.29± 0.05） ,（0.18± 0.07）] were lower in treatment group than those in sham-operated group [（0.67 ± 0.12）, （0.27±0.10）], but Bax positive expression and Sd （0.29± 0.07） were higher in treatment group than those in sham-operated group（S4： 0.12 ± 0. 02）. The proliferation index of treatment group and sham-operated group were 0.12± 0.01 and 0.24 ±0.13 respectively （ P 〈 0. 001 ）. Conclusions Vasectomy and deferent veins ligation on both sides can lead to remarkable atrophy and cell apoptosis in hyperplasia prostatic tissue of pooches, the Bcl-2 and Bax play an important role in the regulation of prostate cell apoptosis.