低剂量毒死蜱重复染毒诱发雄性大鼠生殖毒性及其机制  

Reproductive toxicity of low-level chlorpyrifos repeated exposure and its mechanisms in male rats

作　　者：焦利飞[1] 闫长会[1] 赵君[1] 贾栗[1] 何俊[1] 彭双清[1] 

机构地区：[1]军事医学科学院疾病预防控制所毒理学评价研究中心,北京100071

出　　处：《中国药理学与毒理学杂志》2011年第6期568-575,共8页Chinese Journal of Pharmacology and Toxicology

基　　金：国家科技支撑计划重大项目(2006BAK02A02);国家自然科学基金资助项目(30800929)~~

摘　　要：目的探讨毒死蜱(CPF)低剂量重复染毒对雄性大鼠生殖功能的影响及其可能作用机制。方法健康雄性Wistar大鼠ig给予CPF 1,5和10 mg.kg-1,每日1次。连续染毒12周后取大鼠附睾和睾丸称重计算脏器系数,进行组织病理学、精子数量以及活力及畸形率等检查,测定睾丸碱性磷酸酶(AKP)、酸性磷酸酶(ACP)、γ-谷氨酰转肽酶(γ-GT)和乳酸脱氢酶(LDH)的活性;TUNEL法检测细胞凋亡,免疫组化及Western印迹法检测胱天蛋白酶和Fas,FasL蛋白的表达。结果与正常对照组相比,CPF染毒大鼠睾丸脏器系数显著升高,精子数及精子活力降低,精子畸形率显著升高(P<0.05),睾丸AKP和γ-GT活性抑制明显。组织病理检查显示,睾丸曲细精管疏松和生精细胞减少。CPF染毒组生精细胞凋亡增加(P<0.05)。Fas/FasL蛋白表达量升高。结论 CPF低剂量重复染毒能够诱导雄性大鼠生殖毒性,其作用机制可能与激活Fas/FasL受体途径而引起睾丸生精细胞凋亡有关。OBJECTIVE To investigate effect of chlorpyrifos on reproductive toxicity in male rats and explore the possible mechanisms.METHODS Male Wistar rats were ig given CPF 1,5 and 10 mg·kg-1 or olive oil vehicle（normal control group） daily for 12 consecutive weeks.Testicular and epididymal viscera weight and organ coefficients were calculated,testicular histopathologic changes were evaluated by hematoxylin and eosin（HE） staining,the sperm abnormality,total sperm count and the sperm mobility were examined.The activities of alkaline phosphatase（AKP）,acid phosphatase（ACP）,lactate dehydrogenase（LDH） and γ-glutamyltranspeptidase（γ-GT） were measured.The germ cell apoptosis of testicle was evaluated with TUNEL assay.The expression of factor associated suicide/factor associated suicide ligand（Fas/FasL） and caspase-3 was analyzed by immunohistochemistry and Western blot.RESULTS Compared with normal control group,CPF induced significant increase in the testicular coefficients（P〈0.05） and tendency increases in epididymal viscera.The total sperm counts and the sperm mobility percentage decreased and the sperm abnormality increased in CPF groups（P〈0.05）.There was significant decrease in AKP and γ-GT activities（P〈0.05） in CPF groups.The histopathological examination showed that CPF could lead to atrophia of the contorted seminiferous tubules,and decrease of spermatogenic cell.The TUNEL results showed the significant apoptosis of spermatogenic cells（P〈0.05）.The expression of Fas/FasL and caspase-3 in testis was up-regulated.CONCLUSION Repeated exposures to low dose of CPF may induce the male reproductive toxicity,the Fas/FasL regulated germ cell apoptosis may be one of the mechanism.

关 键 词：毒死蜱 生殖毒性 作用机制 细胞凋亡 FAS/FASL 

分 类 号：R114[医药卫生—卫生毒理学]