非那雄胺通过调控尿道板成纤维细胞增殖和凋亡诱导SD雄鼠发生尿道下裂  

Finasteride induces hypospadias in SD male rats by regulating the proliferation and apoptosis of urethral fibroblasts

作　　者：李飞[1] 安妮妮[1] 彭金普 陈辉[1] 范霞[1] Li Fei;An Nini;Peng Jinpu;Chen Hui;Fan Xia(Guizhou Provincial People’s Hospital,Guiyang 550002,Guizhou,China)

机构地区：[1]贵州省人民医院小儿外科,贵州贵阳550002

出　　处：《贵州医药》2021年第7期1015-1019,共5页Guizhou Medical Journal

基　　金：贵州省科技计划项目(黔科合LH字[2016]7177)。

摘　　要：目的利用非那雄胺构建尿道下裂的SD雄鼠模型,探讨尿道下裂的发生机制。方法 48只SD孕鼠随机分为4组:正常对照组、10 mg/kg.bw、50 mg/kg.bw和100 mg/kg.bw非那雄胺处理组,于妊娠8 d~16 d(GD8~16)进行灌胃,每天1次,每组留下2只孕鼠于分娩1个月后,观察子代雄鼠尿道下裂的阴茎形态。其余孕鼠于GD18取出胎鼠,统计尿道下裂的发生率,HE染色观察阴茎的组织病理学改变。原代培养正常SD雄胎鼠和10 mg/kg.bw非那雄胺处理SD雄胎鼠的尿道板成纤维细胞,通过CCK8法检测细胞的增殖活力,免疫组化和Western blot检测凋亡相关蛋白p53和caspase-3的蛋白表达水平。结果非那雄胺成功诱导SD雄鼠发生尿道下裂,表现为尿道异位开口和包皮分裂,正常对照组、10 mg/kg.bw、50 mg/kg.bw和100 mg/kg.bw非那雄胺处理组的胎鼠尿道下裂发生率分别为0、33.3%、53.6%和66.7%。与正常组相比,10 mg/kg.bw非那雄胺导致尿道板成纤维细胞增殖活力明显增加,差异有统计学意义(P<0.05),凋亡相关蛋白caspase-3和p53的蛋白表达水平明显减少,差异有统计学意义(P<0.05)。结论非那雄胺诱导胎鼠发生尿道下裂与尿道板成纤维细胞增殖增加、凋亡减少相关。Objective To explore the mechanism of hypospadias through establishing hypospadias model of SD rats by finasteride.Methods 48 normal SD pregnant rats were randomly divided into 4 groups which were normal control group,10 mg/kg,50 mg/kg and 100 mg/kg finasteride treatment group.These rats were gavaged with different dose of finasteride from pregnancy GD 8 to16,respectively,once a day,2 pregnant rats in each group were waited for natural labor and observed the penis morphology of the hypospadias of the male offspring on PND30.Then the male fetuses in other pregnant rats were removed at GD18,the incidence of hypospadias was counted,and the histopathological changes of the penis were observed by HE staining.The primary culture of normal and 10 mg/kg.bw finasteride exposure SD male rats urethral plate fibroblasts,then detected cell proliferation activity by CCK8,p53 and caspase-3 protein expression by immunohistochemistry and Western blot.Results Finasteride can induce hypospadias in male SD rats successfully,the phenotype of hypospadias is ectopic urethral opening and cleaved prepuce.The incidence rates of hypospadias are 0,33.3%,53.6%and 66.7%,respectively.Compared with the control group,after finasteride exposure,urethral plate fibroblast proliferation was significantly increased,the protein expression levels of caspase-3 and p53 were decreased obviously.Conclusion Hypospadias induced by finasteride is associated with increased proliferation and decreased apoptosis of urethral fibroblasts.

关 键 词：非那雄胺 尿道下裂 成纤维细胞 

分 类 号：R33[医药卫生—人体生理学] R36[医药卫生—基础医学]