首页|达沙替尼可抑制丙酸睾酮诱导的小鼠前列腺增生

达沙替尼可抑制丙酸睾酮诱导的小鼠前列腺增生

Dasatinib inhibits testosterone propionate-induced benign prostate hyperplasia in mice

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目的 通过动物实验分析达沙替尼对丙酸睾酮(TP)诱导的小鼠良性前列腺增生(BPH)的抑制作用.方法 将美国癌症研究所(ICR)小鼠随机分为正常对照组(n=5)、BPH组(n=5)、非那雄胺组(n=8)、溶剂对照组(n=8)、达沙替尼间断给药组(n=10)和达沙替尼持续给药组(n=10).除正常对照组外,其余组采用皮下注射TP的方法进行BPH小鼠造模,各组分别给予生理盐水、非那雄胺、聚乙二醇400(PEG400)和达沙替尼灌胃治疗,在14 d的造模期和28 d的给药期后处死,解剖小鼠前列腺、脾脏并取血清,比较各组小鼠前列腺质量及前列腺指数(PI)的差异,对前列腺和脾脏进行HE染色,对前列腺做Ki-67免疫组化染色.使用酶联免疫吸附法(ELISA)检测各组小鼠血清双氢睾酮(DHT)和前列腺特异性抗原(PSA)水平.结果 达沙替尼持续给药组和间断给药组的小鼠前列腺质量及PI相较BPH组显著减小(P<0.000 1),血清DHT水平也显著降低(P<0.01),但达沙替尼间断给药组和持续给药组间的小鼠前列腺质量、PI及DHT水平差异无统计学意义(P>0.05);各组间的PSA水平差异无统计学意义(P>0.05).达沙替尼治疗后小鼠前列腺腺体与间质增生的病理表现有明显改善,达沙替尼间断给药组和持续给药组的Ki-67阳性率均显著小于BPH组(P<0.001),但两组间差异无统计学意义(P>0.05).结论 达沙替尼可抑制TP诱导的小鼠BPH,降低血清DHT水平,抑制小鼠前列腺腺体与间质细胞的增殖,且达沙替尼间断给药与持续给药效果一致.
Objective To analyze the therapeutic effects of dasatinib on testosterone propionate(TP)-induced benign prostatic hyperplasia(BPH)in animal experiments.Methods Institute of Cancer Research(ICR)mice were randomly divided into normal control group(n=5),BPH group(n=5),finasteride group(n=8),vehicle group(n=8),dasatinib intermittent administration group(n=10)and dasatinib continuous administration group(n=10).Except for the normal control group,BPH modelling was performed by subcutaneous injection of TP,and the groups were treated with saline,finasteride,polyethylene glycol 400(PEG400)and dasatinib by gavage,respectively.The mice were sacrificed after a 14-day modelling period and a 28-day administration period.The prostate and spleen were dissected,and serum was sampled.Prostate weight was measured and prostate index(PI)was calculated.HE staining was conducted on the prostate and spleen,and Ki-67 immunohistochemical staining was performed on the prostate.Differences in the levels of serum dihydrotestosterone(DHT)and prostate-specific antigen(PSA)were detected with ELISA.Results The prostate weight and PI were significantly reduced in the dasatinib intermittent and continuous administration groups than in the BPH group(P<0.000 1),and the serum DHT level was also significantly reduced(P<0.01),but there were no significant differences in prostate weight,PI and serum DHT between dasatinib intermittent and continuous administration groups(P>0.05),and no significant difference in PSA level among the three groups(P>0.05).After dasatinib treatment,the pathological manifestations of prostate glandular and interstitial hyperplasia were significantly improved;the positive rate of Ki-67 was lower in the dasatinib intermittent and continuous administration groups than in the BPH group(P<0.001).Conclusion Dasatinib can inhibit TP-induced BPH,reduce serum DHT level,and inhibit the proliferation of prostate glandular and interstitial cells in mice.The therapeutic effects of intermittent administration of dasatinib are consistent with those of continuous administration.

benign prostate hyperplasiadasatinibfinasterideKi-67testosterone propionate

顾越、王一惟、徐斌

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上海交通大学医学院附属第九人民医院泌尿外科,上海 200011

良性前列腺增生 达沙替尼 非那雄胺 Ki-67 丙酸睾酮

2024

现代泌尿外科杂志
西安交通大学

现代泌尿外科杂志

CSTPCD
影响因子:1.106
ISSN:1009-8291
年,卷(期):2024.29(12)