过氧基异丙苯对雄性小鼠的自由基毒性与遗传毒性的研究

背景与目的： 过氧基异丙苯是实验室常用的自由基激发剂，本实验旨在了解过氧基异丙苯(Cumene hydroperoxide,CHP)的自由基毒性和遗传毒性，为制造氧化损伤疾病相关动物模型提供参考剂量。 材料与方法： 36只健康昆明种成年雄性小鼠，体重(38.3±7.8) g , 随机分为4 组。灌胃染毒，染毒剂量分别为2 000、500、125和0 μg/kg。每天1 次，每周5 d，共计40 d。实验结束后处死小鼠，观察小鼠骨髓微核、精子畸变率，测定睾丸组织匀浆中丙二醛(Malondialdehyde，MDA)、 总超氧化物歧化酶(Total superoxide dismutase，T-SOD)、还原型谷胱甘肽(Glutathion，GSH)的水平。 结果： CHP染毒各组小鼠体重有程度不同的减轻，随染毒剂量的增加，睾丸组织匀浆中MDA含量逐渐增加，T-SOD活力、 GSH含量逐渐降低，其中2 000 μg/kg体重染毒组睾丸组织匀浆中MDA含量与对照组比较差异有统计学意义(P<0.01)，500 μg/kg染毒组GSH含量、SOD活力与对照组比较差异有统计学意义(P<0.05)；骨髓嗜多染红细胞微核及精子畸变率增高，2 000 μg/kg染毒组与对照组比较差异有统计学意义(P<0.01)。 结论： CHP对昆明种小鼠具有很强的自由基毒性和遗传毒性，CHP的自由基毒性引发的氧化损伤可能是其遗传毒性的重要机制。

The Study of Free Radical Toxicity and Genotoxicity of CHP on Male Mice

BACKGROUND ＆ AIM： To explore the relationship between the free radical toxicity and genotoxicity of cumene hydroperoxide(CHP). MATERIAL AND METHODS： 36 mice were divided into four groups randomly. Their average body weight was (38.3±7.8) g. The CHP exposure doses were 2 000，500，125 and 0 μg/kg by gavage daily，five days in a week for 40 days. The change of the marrow micronucleus in polychromatic erythrocytes(PCE)and sperm deformity ratio were detected. The contents of malondialdehyde(MDA)，total superoxide dismutase(T-SOD) and reduced glutathion(GSH) in homogenate of testis were tested. RESULTS: The body weight of mice exposed to CHP had decreased to different degrees. With the increasing dose of CHP, the contents of MDA in testis homogenate were increased and the contents of T-SOD and GSH were gradually decreased. The MDA in testis homogenate of mice exposed to 2 000 μg/kg CHP was significantly higher than that of control group(P<0.01). The GSH and the T-SOD in testis homogenate of mice exposed to 500 μg/kg CHP were markedly lower than that of control group(P<0.05). The change of the marrow micronucleus in PCE and sperm deformity ratio were increased. Mice exposed to 2 000 μg/kg CHP had obvious change compared with that of control group(P<0.01). CONCLUSION: CHP twed strong free radical toxicity and genotoxicity on mice, the oxidative injury caused by free radical of CHP might induce its genotoxicity.