摘要
目的 探索低剂量醋酸棉酚 (GA)组合甲基睾酮 (MT)及炔雌醇 (EE)抗雄性生育作用的可行性及优化方案。 方法 采用Wistar雄性大鼠 ,A组喂 1%甲基纤维素、B组喂GA 12mg·kg-1·d-1作对照 ;C组喂 (GA 12 +MT 2 0 +EE 0 .1)mg·kg-1·d-1;D组喂 (MT2 0 +EE 0 .1)mg·kg-1·d-1。于C组 6周、D组 8周抗生育起效后 ,以低剂量GA(12mg·kg-1·d-1)维持药效。交配试验检测生育力 ,取睾丸、附睾、内脏及血样进行组织学及生化检查 ,观察生育恢复和F1仔鼠发育情况。 结果 C组用药第 6周 10 0 %雄鼠不育 ,低剂量GA可继续维持抗生育效果 ,停药 6周生育力全部恢复 ;D组用药 8周达 10 0 %不育 ,低剂量GA不能维持不育。实验期间未发现明显的毒副反应。 结论 口服低剂量GA和MT及EE起效后并以低剂量GA维持药效用药方案 ,是一种起效快、可维持、安全。
Objective: To study the feasibility and optimal regimen of oral low dose gossypol acetate (GA) combined with methyltestosterone (MT) plus ethinyl estradiol (EE) for contraception in male rats. Methods:Wistar rats were randomly assigned into four groups, 20 in each group Groups A and B were administered daily with 1% methyl cellulose and GA (12 mg·kg -1 ·d -1 ) suspended in 1% methyl cellulose, respectively. Group C and D took firstly (GA12 + MT20+ EE 0.1) mg·kg -1 ·d -1 or (MT20 + EE 0.1) mg·kg -1 ·d -1 , in a suspension with 1% methyl cellulose, via gastric intubation. After antifertility effect were initiated, GA was served while MT+EE were withdrawn in groups C and D. Fertility test, morphologic influences in sperm, testes, epididymides and viscera, and biochemical changes were used to determine the fertility restoration in treated rats. The growth and development of F1 generation of the rats would also be examined in a series of behavioral tests. Results: In present study, ten of ten rats were infertile in the group C at sixth week of treatment. Afterward the fulfilled infertility indexes could be maintained with GA (12 mg·kg -1 ·d -1 ) only. Six weeks after cessation of treatment, all treated rats recovered their fertility. In group D, eight of ten rats were infertility at 6th week of treatment and all at 8th week of treatment, but the infertility could not be kept with the GA only later on. Moreover, no adverse effects were found in our experiments. Conclusion: The regimen of oral low dose GA and MT plus EE firstly could successfully induce antifertility effect in a short term and the effect could completely be maintained by using low dose GA only. The regimen seems to be a safe, optimal, long term, reversible contraceptive method for male.
出处
《生殖医学杂志》
CAS
2004年第2期91-95,共5页
Journal of Reproductive Medicine
基金
国家自然科学基金 (3 0 170 985 )
国家计划生育委员会C1类项目(2 0 0 2 C1 M 0 5 )
关键词
棉酚
甲基睾酮
炔雌醇
抗生育
雄性大鼠
Gossypol
Methyltestosterone
Ethinyl estradiol
Antifertility effect
Male rats
