三个品系小鼠白消安无精子症模型的比较

Establishing azoospermia model with busulfan in three strains of mice

目的通过对ICR、NIH、Balb／c三个品系雄性小鼠腹腔单次注射白消安，寻求成功建立小鼠无精子症模型的最佳剂量。方法三个品系小鼠分批次进行实验共l096只，分别给予白消安45、40、35和30mg／kg四个剂量，40d后存活小鼠为模型动物，以正常动物为对照（无处理）。造模后连续观察2个生精周期共70d，观察记录小鼠体重变化和死亡情况。分别于造模后0．5、5、7．5、10周取材，以附睾精子质量检测和睾丸组织形态学观察评价造模效果和生精能力恢复情况。结果无精子症模型动物外观体征明显改变，以NIH小鼠变化更为明显；NIH小鼠30mg／kg白消安无精子症模型造模失败，而35、40和45mg／kg白消安在所研究的三个品系小鼠均可成功建立无精子症模型；动物死亡率在NIH小鼠呈显著剂量效应关系（P〈0．01），45mg／kg白消安剂量组最高，为69．2％；在NIH和ICR小鼠，35mg／kg剂量组存活率分别为71．3％（194／272）和94．4％（51／54），均显著高于40mg／kg剂量组（P〈0．01）。结论使用临界剂量35mg／kg白消安在3个品系小鼠均可成功建立无精子症模型，并较40mg／kg和45mg／kg白消安组造模成功动物的成活率明显提高，提示可以不采用通常建议的40～45mg／kg剂量。自消安无精予症小鼠模型在2个生精周期（70d）内维持基本稳定，处于无精子症或低生精能力状态。

Objective： To obtain the optimal dose of busulfan for establishing azoospermia model in three strains of mice. Methods： A total of 1 096 male ICR, NIH and Balb/c strains of mice were intraperitoneally injected with 45,40,35 or 30 mg/kg busulfan. Body mass and mortality were observed daily for 70 days. The sperm quality and testicular morphology were observed at 0.5,5,7.5 and 10 weeks after busulfan injection to evaluate the modeling effect and spermatogenesis status. Results： The 30 mg/kg busulfan was failed to establish the azoospermia model,but busulfan at dose of 35,40 and 45 mg/kg could induce azoospermia in the three strains of mice. Compared with the normal mice,the appearance signs were obviously changed, and the weight was significantly reduced in the model animals,especially in NIH mice. The mortality was in a dose-dependent manner in NIH mice（P〈0.01）, and the highest mortality rate was 69.2% at dose of 45 mg/kg in NIH mice. The survival rate was 71.3%（194/272） and 94.4% （51/54）at dose of 35 mg/kg in ICR and NIH mice respectively, which was significantly higher than that at dose of 40 mg/kg（P〈0.01）. Conclusions： Admin the s dose. or 45 urvival rate at dose It indicates that th istration of 35 mg/kg busulfan can successfully establish azoospermia model, and of 35 mg/kg was significantly increased compared with 40 mg/kg or 45 mg/kg e busulfan dose used for establishing azoospermia model should not be 40 mg/kg mg/kg,which is generally recommended before.