非那雄胺诱导尿道下裂小鼠模型的实验研究及相关机制探讨  

Experimental study and mechanism of finasteride induced hypospadias in mice

作　　者：范霞[1] 李飞[1] 黄璜[1] Fan Xia;Li Fei;Huang Huang(Department of Pediatrics,Guizhou People's Hospital,Guiyang,Guizhou,550000,China)

机构地区：[1]贵州省人民医院儿外科

出　　处：《当代医学》2020年第8期4-7,共4页Contemporary Medicine

摘　　要：目的观察非那雄胺是否能诱导尿道下裂小鼠模型的建立,并探讨相关作用机制。方法将30只C57BL/6孕鼠随机分为低剂量实验组、高剂量实验组和对照组,每组10只,于孕11、12、13、14、15、16 d给予非那雄胺10 mg/kg、20 mg/kg及植物油0.5 mL/kg干预,孕期根据大鼠体质量调整药物剂量。观察出生小鼠睾丸的位置、前列腺发育、乳头退化延迟情况,并记录肛生殖窦距离(AGD)。出生后第5周,检测新生鼠有无尿道下裂及隐睾。采用WB检测法检测小鼠生殖结节中p-Akt、p-mTOR、Beclin-1蛋白表达情况。结果出生时对照组、低剂量实验组、高剂量实验组AGD分别为(:1.54±0.06)mm、(0.92±0.11)mm、(0.79±0.14)mm,乳头数分别为5.1、10.6、11.6个。出生后第5周对照组无尿道下裂与隐睾发生,低剂量实验组、高剂量实验组雄性小鼠尿道下裂发生率分别为31.14%、61.40%,隐睾发生率分别为21.31%、43.86%,低剂量实验组、高剂量实验组尿道下裂发生率及隐睾发生率比较差异均有统计学意义(P<0.05)。WB检测显示,对照组、低剂量实验组、高剂量实验组生殖结节中p-Akt蛋白相对表达量为(1.25±0.32)、(0.62±0.11)、(0.48±0.06),生殖结节中p-mTOR蛋白相对表达量为(2.58±0.24)、(2.04±0.32)、(1.06±0.08),Beclin-1蛋白相对表达量为(0.12±0.06)、(0.58±0.10)、(0.86±0.07),与对照组比较,低剂量实验组、高剂量实验组生殖结节中p-Akt、p-mTOR蛋白表达量降低(P<0.05),Beclin-1蛋白表达量升高(P<0.05)。结论非那雄胺能够诱导出C57BL/6小鼠发生尿道下裂模型,干预剂量增大后其尿道下裂和隐睾发生率也随之升高,其机制与抑制小鼠生殖结节中P13K/Akt/mTOR通路的磷酸化,增加自噬水平有关。Objective To observe whether finasteride can induce hypospadias in mice and to explore its mechanism. Methods 30 pregnant C57BL/6 mice were randomly divided into low-dose experimental group, high-dose experimental group and control group, 10 mice in each group,which were given finasteride 10 mg/kg, 20 mg/kg and vegetable oil 0.5 mL/kg on the 11th, 12th, 13th, 14th, 15th and 16th day of gestation. The drug dosage was adjusted according to the weight of rats during pregnancy. The location of testis, the development of prostate and the delayed degeneration of papilla were observed, and the distance between anus and genital sinus(AGD) was recorded. At the 5th week after birth, hypospadias and cryptorchidism were detected in neonatal rats. WB method was used to detect the expression of p-Akt, p-mTOR and Beclin-1 in reproductive nodules of mice. Results At birth, the AGD of control group, low dose experimental group and high dose experimental group were(1.54±0.06) mm、(0.92±0.11) mm、(0.79±0.14) mm, respectively, the number of nipples were 5.1, 10.6, 11.6. There was no hypospadias and cryptorchidism in the control group at the 5 th week after birth. The incidence of hypospadias and cryptorchidism were 31.14% in the low dose group and 61.40% in the high dose group. The incidence of cryptorchidism was 21.31% and 43.86%, respectively. There was significant difference in the incidence of hypospadias and cryptorchidism between the low dose group and the high dose experimental group(P<0.05). WB assay showed that the relative expression of p-Akt protein in reproductive nodules of control group, low-dose experimental group and high-dose experimental group was(1.25±0.32),(0.62±0.11),(0.48±0.06), the relative expression of p-mTOR protein in reproductive nodules was(2.58±0.24),(2.04±0.32),(1.06±0.08), and the relative expression of Beclin-1 protein was(0.12±0.06),(0.58±0.10),(0.86±0.07). Compared with the control group, the expression levels of p-Akt and pmTOR in the low-dose and high-dose reproductive nodules in th

关 键 词：非那雄胺 尿道下裂 建模 P13K/Akt/mTOR通路 自噬 

分 类 号：R695[医药卫生—泌尿科学] R-332[医药卫生—外科学]