美他多辛对大鼠的雄性生殖毒性

THE MALE REPRODUCTIVE TOXICITIES OF METADOXINE ON RATS

目的 :观察美他多辛对雄性大鼠的生殖毒性。 方法 :雄性SD大鼠每天经口给美他多辛0、500、1000、2000mg/kg,连续2周。分别于末次给药后24h和停药3周后各处死一半动物 ,检查睾丸和附睾等雄激素依赖组织的重量 ,计算脏/体比 ,并观察精子数量、活动度、存活率及精子形态。结果 :500mg/kg组无论给药后24h还是停药3周后观察 ,各项指标与对照组比较均无显著性差异。末次给药后24h观察 ,除了1000和2000mg/kg组包皮腺的脏/体比与对照组有轻度但有显著意义地降低(P<0.05)外 ,其余指标均无显著性差异。停药3周后观察 ,1000mg/kg组提肛肌/前列腺比、附睾/体重比降低 ,精子畸形率增高 ;而2000mg/kg组睾丸、附睾、包皮腺的脏/体比和提肛肌/前列腺比均下降 ,精子数量减少 ,存活率降低 ,活动度下降。结论 :雄性大鼠经口摄入美他多辛1000mg/kg以上 ,连续2周 ,对生殖系统有明显的毒性 。

Purpose: To observe the effect of metadoxine on m ale reproductivetoxicity on rats. Methods: Male Sprague_Dawley rat s were administrated orally with metadoxine at 0, 500, 1 000 , and 2 000 mg / kg once daily for 2 weeks. Half of the animals were sacrificed 24 h after the end of treatment an d the others were examined with a 3_week interval time. The organ ratio of testis, epididymidis, and other androgen depend ent tissues were measured. Sperm count, mortality, activity, mor phology were also analyzed. Results: There were not any signif icant changes in all the parameters examined in 500 mg / kg group either at the end of treatment or 3 weeks after trea tment. Twenty_four hours after the end of treatment, no signif icant abnormalities were observed except that the organ ratio of prepuse gland slightly but significantly decreased in 1 000 and 2 000 mg / kg compared with the control (P <0.05). Three weeks after treatment, however, the ratios of cr emaster muscle / prostate gland and epididymidis / body weight decre ased, and the frequency of sperm abnormality increased significa ntly in 1 000 mg / kg group. Dramatic decline in organ ratio s of testis, epididymidis, and prepuse gland, and the ratio of cremaster muscle / prostate gland, sperm count, the percentage of survival and activity of sperm were observed in 2 000 mg / kg group. Conclusion: Male reproductive toxicities were indu ced by exposure with metadoxine at 1 000 mg / kg or higher for two weeks in Sprague_Dawley rats, and the damages seen to be progressive.