摘要
目的观察不同剂量三氧化二砷(As2O3)对成年大鼠生精细胞凋亡、端粒酶活性端粒酶逆转录酶(telomerase reverse transcriptase,TERT)mRBA表达的影响。方法40只健康雄性SD大鼠随机分成4组,分别为0.375,0.75,1.5 mg/kg 3个染毒组和对照组,灌胃法连续给药16周。采用末端转移酶介导的dUTP缺口末端标记法(TUNEL)法检测大鼠生精细胞凋亡情况,免疫组化法检测大鼠生精细胞端粒酶活性的表达,核酸原位杂交检测睾丸生精细胞TERT mRNA的表达。结果与对照组比较,中剂量组和高剂量组生精细胞凋亡指数(AI)均显著升高(P<0.01);与对照组比较,中、高剂量组大鼠生精细胞端粒酶阳性表达明显降低(P<0.01);与对照组比较,中、高剂量组大鼠生精细胞TERT mRNA明显降低(P<0.01);生精细胞端粒酶活性的表达与生精细胞凋亡之间呈显著负相关(r=-0.896,P<0.01);生精细胞TERT mRNA的表达与端粒酶活性之间呈显著正相关(r=0.832,P<0.01)。结论一定剂量的As2O3可通过抑制生精细胞TERT mRNA的表达,使端粒酶活性降低从而导致生精细胞凋亡增加,产生生殖毒性。
Objective To observe the apoptosis, expression of telomerase activity and telomerase reverse transcriptase （TERT） mRNA in spermatogenie cells after anisodoses arsenic （As2O3） administration in the testes of adult male rats. Methods Forty health male Sprague - Dawle rats were divided randomly into four groups and were administered respectively with 0 （control group）, 0. 375, 0.75, 1.5 mg/kg As2O3 water solution by intragastric administration consecutively for 16 weeks. Ternimal dexynucleotidyl tranferase- mdiated dUTP- biotin nick end labeling （TUNEL） was used to measure the apoptosis of spermatogenic cells of rats treated with arsenic. The telomerase activity and TERT mRNA expression in rat testicle spermatogenic cells were tested by method of immunohistochemistry （ICH） and nucleic acid hybridization in situ （ISH）. Results The apoptosis index （AI） of middle dose group and high dose group significantly increased compared with that in the control group （P 〈 0.01 ）. The expression of telomerase activity in middle dose group and high dose group decreased significantly compared with that in the control group （P 〈 0.01 ）. The expression of TERT mRNA in middle dose group and high dose group decreased significantly compared with that in the control group （ P 〈 0.01 ）. The negative correlation was significant between apoptosis and telomerase activation of spermatogenic cells （ r = - 0. 896, P 〈 0.01 ）. The positive correlation was significant between telomerase activity and TERT mRNA expression of spermatogenic cells （r = 0. 832, P 〈 0.01 ）. Conclusion One of the mechanisms of male reproduction toxicity of As2O3 might be that telomerase activity is inhibited by the down regulation of TERT mRNA expression, which induces the increase of apoptosis of spermatogenic cells and decrese of quantity of sperm cells.
出处
《中国公共卫生》
CAS
CSCD
北大核心
2008年第11期1382-1384,共3页
Chinese Journal of Public Health
基金
贵州省国际科技合作重点项目(黔科合J字[2006]2078号)
关键词
AS2O3
端粒酶逆转录酶
生精细胞
凋亡
As2O3
telomerase reverse transcfiptase
spermatogenic cells
apoptosis
