摘要
目的研究1,3-丁二烯的活性中间代谢产物1,2,3,4-二环氧丁烷(1,2,3,4-diepoxybutane,DEB)对小鼠睾丸生殖细胞的损伤。方法成年雄性昆明小鼠分为溶剂对照组(PBS)、低剂量(17 mg/kg)DEB染毒组和高剂量(42.5 mg/kg)DEB染毒组。采用腹腔注射染毒,于第1、3、5天间隔注射3 d,初次染毒后的第21天采样。比较睾丸系数、精子密度、精子活动度以及睾丸组织的病理学改变。采用流式细胞仪进行睾丸细胞周期及DNA倍型分析。采用化学比色法检测小鼠肝组织氧化和抗氧化能力的改变。结果与溶剂对照组相比,各染毒组小鼠的睾丸系数及精子密度均有下降,且高剂量DEB染毒组明显降低(P<0.05)。与溶剂对照组相比,DEB染毒小鼠的极慢或不动的精子比例显著升高(P<0.05,P<0.01)。细胞周期分析结果显示,高剂量DEB染毒组的单倍体和二倍体细胞比例降低,而四倍体细胞比例升高,同时G2/M期细胞比例升高,差异均有统计学意义(P<0.05)。随着染毒剂量增加,睾丸结构受损,肝组织的MDA水平增加,而SOD和GSH-Px水平降低,其中高剂量DEB染毒组的变化具有统计学差异(P<0.05)。结论 DEB染毒可以造成小鼠睾丸细胞损伤,干扰生精细胞的周期进程,氧化应激可能是DEB诱导生殖细胞损伤的原因之一。
Objective To determine the toxic effects of 1,2,3,4-diepoxybutane （ DEB ）, a metabolic intermediates of 1,3-butadiene, on germ cells of male mice. Methods Male Kunming mice were randomly divided into 3 groups, including solvent control group （PBS）, DEB low dose （17 mg/kg） exposure group and high dose （42.5 mg/kg） exposure group. Each mouse was intraperitoneally treated for 3 times at an interval of 48 h. The mice were sacrificed on day 21 after the first injection. The testis coefficient, sperm density, sperm motility and pathological changes of the testis tissue were examined. The cell cycle distribution and DNA content of testicular cells were analyzed by flow cytometry. The quantity of malodialdehyde （MDA） and the activity of glutathione peroxidase （GSH-Px） and superoxide dismutase （SOD） in liver were detected by chemical colorimetry. Results Compared with control group, the testis coefficient and sperm density were decreased in DEB-treated groups, with 42.5 mg/kg DEB group reduced more significantly （P 〈 0.05）. And the sperm percentage of the extremely slow or motionless was obviously increased （P 〈 0. 05 or P 〈 0. 01 3 in groups treated with low or high dose of DEB. Flow cytometry showed that the percentages of haploid and diploid cells were significantly lower in 42.5 mg/kg group than control group （ P 〈 0.05 ）, whereas the percentages of tetraploid cells and G2/M cells were significantly higher than control （P 〈 0. 05 ）. Furthermore, with the increase of DEB treatment, the impaired testicular structure was observed. When compared with control group, the level of MDA was higher （P 〈 0.05 ）, but the activities of GSH-Px and SOD were lower （ P 〈 0.05） in the liver tissue of mice treated with 42.5 mg/kg DEB （P 〈 0.05）. Conclusion DEB exerts reproductive toxic effects on sperm cells, induces disturbance of cell cycle progression of spermatogenic cells, and leads to the oxidative stress in mice.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2015年第9期881-885,共5页
Journal of Third Military Medical University
基金
国家自然科学基金面上项目(81273105)
重庆市自然科学基金一般项目(CSTC2012jjA 0276)~~
