机构地区:[1]南京医科大学附属南京妇幼保健院妇科,江苏南京210004 [2]南京医科大学江苏省应用毒理重点实验室,江苏南京210029
出 处:《中华男科学杂志》2008年第11期968-972,共5页National Journal of Andrology
基 金:国家"九五"医学科技攻关项目(96-906-04-11);国家攀登项目子课题(2000504)
摘 要:目的:研究辛硫磷(Pho)与氰戊菊酯(Fen)对雄性大鼠生精过程的联合毒性作用。方法:根据统计学三个剂量水平的析因分析方法(3×3)研究Pho与Fen,以对照组及Pho和Fen的半数致死量(LD50)的1/250 LD50(5.9、2.4 mg/kg)和1/50 LD50(29.4、12.0 mg/kg)分别作为低剂量组、高剂量组设计成三个剂量水平。将135只成年SD大鼠随机分为9组,即分为对照组(0 mg/kg);Pho组:(5.9、29.4 mg/kg);Fen组:(2.4、12.0 mg/kg);Pho+Fen组:(5.9+2.4、5.9+12.0、29.4+2.4、29.4+12.0 mg/kg)。将不同剂量的Pho、Fen、Pho+Fen,每日分别对雄性成年SD大鼠连续灌胃,染毒15 d和30 d。应用RIA法测定大鼠血清中FSH、LH、T和睾丸匀浆中T的水平,同步测定睾丸组织中的睾丸标志酶ACP、γ-GT的活性,并采用精子头计数法观测每日精子生成量(Spr)的变化。结果:染毒15 d,Pho与Fen混配农药对血清中LH、FSH有明显的交互作用(P<0.05),生殖毒性相互影响,数据分析表明LH随着剂量的增加在高剂量组(29.4+12.0 mg/kg)联合作用呈现为协同作用,而FSH的水平变化则随剂量增加表现为拮抗作用(P<0.01)。染毒30 d,混配农药(Pho+Fen)对睾丸匀浆中的T含量存在显著的交互作用(P<0.05),联合作用表现为协同作用。在染毒15、30 d,随着剂量的增加,Pho和Fen均可引起Spr的减少及γ-GT和ACP的活性降低,但Pho与Fen的混配对Spr、ACP、γ-GT无明显的交互作用(P>0.05),联合作用表现为相加作用。结论:在已知Pho和Fen均对生精过程具有损害作用的前提下,本研究表明Pho和Fen对生精过程的联合作用表现为其对生精过程的损害与所暴露的剂量水平和时间均有明显的关联性,联合作用主要表现为协同作用和相加作用,有明显的增毒效应。Objective: To assess the joint toxicity of phoxim (Pho) and fenvalerate (Fen) on the spermatogenesis of male rats and to clarify its mechanism. Methods : Based on the three administrative levels of factorial analysis (3 × 3) of Pho and Fen, i.e. their half lethal dose (LDSO) 1/250 LDSO (5.9, 2.4 mg/kg) and 1/50 LDSO (29.4, 12.0 mg/kg) and the control, 135 adult male SD rats were randomly assigned to 9 groups, the control (0.0 mg/kg), Pho (5.9, 29.4 mg/kg), Fen (2.4, 12.0 mg/kg), Pho + Fen (5.9 +2.4, 5.9 + 12.0, 29.4 +2.4, 29.4 + 12.0 mg/kg ), and treated intragastrically with different doses of Pho, Fen and Pho + Fen for 15 and 30 days. The levels of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and testis homogenate T were determined by radioimmunoassay (RIA), the activity of testicular marker enzymes such as acid phosphatases (ACP) and gamma-glutamyl transpeptidase (γ-GT) examined, and the sperm head count measured for the changes of daily sperm production (Spr). Results: At 15 days, obvious interaction was observed between Pho and Fen in both serum LH and FSH (P 〈 0.05), as well as between their reproductive toxicities. With the increase in doses, the joint action was synergistic in LH (P 〈 0. 05) and antagonistic in FSH (P 〈0. 01 ) at a high dose ( 29.4 + 12.0 mg/kg). At 30 days, marked interaction between Pho and Fen was noted in the content of homogenate T (P 〈 0.05), with a joint synergistic effect. At 15 and 30 days, with the increase of doses, both Pho and Fen reduced Spr and the activity of ACP and γ-GT, but Pho + Fen showed no obvious interaction in them ( P 〉 0. 05 ), and their joint action was an additive effect. Conclusion : Pho and Fen jointly impaired spermatogenesis in a dose- and time-dependent manner. Their joint action exhibited mainly as a synergistic effect, an additive effect and increased toxicity.
分 类 号:R114[医药卫生—卫生毒理学]
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