不同剂量氟他胺诱导小鼠建立尿道下裂及隐睾模型研究

Model establishment of hypospadias and cryptorchidism induced by different dosages of flutamide in mice

目的采用雄性激素受体拮抗剂氟他胺建立小鼠尿道下裂与隐睾模型,为造模所需氟他胺的剂量范围提供理论及实验依据。方法 7～8周龄BALB/c小鼠54只,体质量(20±1)g,分为A、B、C、D、E、F 6组,每组9只。在母鼠孕第12～21天,每日经皮下注射给予氟他胺,连续10 d,A、B、C、D、E组每日剂量依次为100、200、300、400和500 mg.kg-1,F组不给药为对照组。出生后5周观察有无尿道下裂与隐睾。从每组取3只雄性仔鼠解剖观察睾丸细胞的形态学变化。结果 A、B、C、D组F1代雄性小鼠尿道下裂发生率分别为45.0%、61.1%、79.9%、47.1%,隐睾发生率分别为0.0%、0.0%、30.4%、41.2%,E组母鼠均流产,F组无尿道下裂与隐睾发生。隐睾组织的形态学变化为生殖细胞数减少,大量多核细胞,曲精小管直径减小。结论氟他胺能够诱导出F1代小鼠发生尿道下裂及隐睾模型,并且随着剂量的加大,尿道下裂和隐睾发生率也有所提高,但其理想剂量为300 mg.kg-1.d-1。

Objective The model of hypospadias and cryptorchidism were established by flutamide which androgen receptor antagonist in mice,and to provide theoretical and experimental basis for the dosage range of flutamide needed in the experiment. Methods Fifty-four BALB/c mice which 7-8 weeks of age were bought,body weight was（20±1）g,and divided into 6 groups of A,B,C,D,E and F,each group was 9 cases.At 12-21 days of gestation in mother rat,flutamide was given by subcutaneous injection every day,for 10 days.Daily dose of A,B,C,D and E group was 100,200,300,400 and 500 mg·kg-1,F group did not give medicine as control group.To observe that whether hypospadias and cryptorchidism existed after 5 weeks of birth.Three male and young mice were took and dissected from each group,and to observe the morphological changes of testicular cells. Results The incidence of hypospadias in groups of A to D was 45.0%,61.1%,79.9%,47.1%.And incidence of cryptorchidism was 0.0%,0.0%,30.4%,41.2%.The mother mice of group E were all abortion and group F was no hypospadias and cryptorchidism.The morphology changes of cryptorchidism tissue were the germ cells decrease,multinucleated cells increase largely and the diameter of seminiferous tubule decrease. Conclusion The model of hypospadias and cryptorchidism could be established by flutamide in mice of F1 generation.And along with the dose of increasing,the incidence of hypospadias and cryptorchidism are increase,but the ideal dosage is 300 mg·kg-1·d-1.