目的 探究萘普替尼对雄性大鼠睾丸形态结构及附睾精子质量的影响。方法 将30只雄性SD大鼠随机分为30和70 d两组，每组又分为对照组和萘普替尼低、高剂量组（0.75、3.00 mg/kg），ig给药，每天给药1次，给药体积10 mL/kg。每天进行1次症状观察，每周称量一次体质量，大鼠分别于给药35和70 d后次日处死，肉眼检查各脏器有无异常，检测双侧睾丸质量和横径、附睾尾精子数量和活力，睾丸固定进行组织病理学检查。结果 萘普替尼高剂量组动物均从给药第14天开始，出现腹泻、脱毛、口鼻眼处有红色分泌物，随着给药天数的增加，症状加重；给药70 d组其中1只动物于给药60 d开始出现血尿症状。给药35 d组大鼠从给药21 d开始，给药70 d组从14 d开始，高剂量大鼠体质量明显低于同期对照组（P<0.01）。与对照组比较，给药组雄鼠的双侧睾丸绝对质量和脏器指数、睾丸横径、附睾尾精子数量和活力及睾丸组织病理学检查并未随给药剂量的增加和给药时间的延长而出现明显变化。结论 萘普替尼对雄性大鼠的睾丸组织及精子质量无明显影响。

Objective To investigate the effects of neptinib on testicular morphosis and epididymal sperm quality of male rats. Methods A total of 30 male SD rats were assigned to blank control group (0 mg/kg), low dose group (0.75 mg/kg), and high dose group (3 mg/kg) in a random manner. The test substance was administered by gavage, and the administration volume was 10 mL/kg. The frequency of administration was once daily. All rats was made general clinical observation once daily, and weighed once a week. All rats were sacrificed on the next day after 35 d and 70 d of dosing, and all organs were examined macroscopically for any structural abnormalities with the naked eyes. Both testes were weighed and calculated relative weights. Transverse diameter of both testes was measured. Sperm numbers and motility were assessed in the cauda epididymis. The testes were fixed for histopathological examination. Results From the 14th d of administration, the rats in the high dose group of neptinib had diarrhea, hair removal, and red secretions in the mouth and nose, and the symptoms increased with the increase of the number of dosing days. In the 70 d of dosing group, one animal began to appear hematuria at 60 d. Body weight of the high-dose rats in the 35 d group starting from the 21st d of administration, and in the 70 d group starting from the 14st d were both significantly lower than that of control group (P<0.01). Compared with the blank control group, there were no dose-or duration-related obvious changes in the absolute weight and visceral index of tests, the transverse diameter of testes, the number and motility of sperm, and testicular histopathology in treatment groups. Conclusion Neptinib has no obvious toxic effects on testicular morphosis and sperm quality in male rats.

国家科技重大新药创制项目（2015ZX09501004）；天津市科技计划项目（16PTGCCX00090）