目的 探究萘普替尼對雄性大鼠睪丸形態(tài)結(jié)構(gòu)及附睪精子質(zhì)量的影響。方法 將30只雄性SD大鼠隨機分為30和70 d兩組，每組又分為對照組和萘普替尼低、高劑量組（0.75、3.00 mg/kg），ig給藥，每天給藥1次，給藥體積10 mL/kg。每天進行1次癥狀觀察，每周稱量一次體質(zhì)量，大鼠分別于給藥35和70 d后次日處死，肉眼檢查各臟器有無異常，檢測雙側(cè)睪丸質(zhì)量和橫徑、附睪尾精子數(shù)量和活力，睪丸固定進行組織病理學(xué)檢查。結(jié)果 萘普替尼高劑量組動物均從給藥第14天開始，出現(xiàn)腹瀉、脫毛、口鼻眼處有紅色分泌物，隨著給藥天數(shù)的增加，癥狀加重；給藥70 d組其中1只動物于給藥60 d開始出現(xiàn)血尿癥狀。給藥35 d組大鼠從給藥21 d開始，給藥70 d組從14 d開始，高劑量大鼠體質(zhì)量明顯低于同期對照組（P<0.01）。與對照組比較，給藥組雄鼠的雙側(cè)睪丸絕對質(zhì)量和臟器指數(shù)、睪丸橫徑、附睪尾精子數(shù)量和活力及睪丸組織病理學(xué)檢查并未隨給藥劑量的增加和給藥時間的延長而出現(xiàn)明顯變化。結(jié)論 萘普替尼對雄性大鼠的睪丸組織及精子質(zhì)量無明顯影響。

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.

國家科技重大新藥創(chuàng)制項目（2015ZX09501004）；天津市科技計劃項目（16PTGCCX00090）