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

作　　者：顾越 王一惟[1] 徐斌[1] GU Yue;WANG Yiwei;XU Bin(Department of Urology,Shanghai Ninth People s Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200011,China)

机构地区：[1]上海交通大学医学院附属第九人民医院泌尿外科,上海200011

出　　处：《现代泌尿外科杂志》2024年第12期1104-1109,共6页Journal of Modern Urology

摘　　要：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<0.0001),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<0.0001),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 wit

关 键 词：良性前列腺增生 达沙替尼 非那雄胺 KI-67 丙酸睾酮 

分 类 号：R697.32[医药卫生—泌尿科学]