目的研究农药氰戊菊酯(Fen)对雄性生殖功能系统的时间毒性及机制。方法选择健康雄性SD大鼠49只,以光照起点时间定为ZT 0,将自然时间转换为授时时间(ZT)。将大鼠分为对照组和6个Fen染毒组。Fen染毒组:以mg/kg BW的灌胃剂量分别在ZT 02、ZT 06、ZT 10、ZT 14、ZT 18、ZT 22授时时间点给药,连续30d;对照组给予等量食用调和油。制作睾丸HE病理切片,测定每日精子生成量(DSP)、检测精子活率(LSR)、畸形率(ASR)及睾丸标志酶(ACP和γ-GT)活性,应用RIA法测定大鼠睾丸中的睾酮(T)和雌二醇(E2)水平。结果 (1)与对照组相比,Fen引起大鼠睾丸组织病理性改变,且在ZT 18时损伤最为严重;Fen降低了雄性大鼠每日精子生成量、精子活率、睾丸标志酶活性和睾酮含量,增加了雌二醇含量和精子畸形率。(2)Fen引起大鼠雄性生殖指标每日精子生成量、精子活率、睾丸磷酸酶活性的变化具有昼夜节律性,其敏感时间点分别为:ZT 04、ZT 14、ZT 23。结论 Fen对雄性生殖指标具有毒性并在每日精子生成量、精子活率、睾丸磷酸酶活性中表现出一定的昼夜时间节律性。
Objective To study the chronotoxicity and mechanism of fenvalerate(Fen) on the male reproductive system.Methods Forty-nine healthy clean SD rats in a 12h∶12h light-dark photoperiod,which were divided into seven groups:control group and six Fen groups(Fen 2,Fen 6,Fen 10,Fen 14,Fen 18,Fen 22).Fen groups were administered by intra-gastric injection of Fen(12 mg/kg BW) respectively at corresponding zeitgeber time(ZT 02,ZT 06,ZT 10,ZT 14,ZT 18,ZT 22) for 30 days.The control group rats were administered with equal volume of edible blend oil.One side testicular was used to make HE paraffin slice.Germ cell(Daily sperm production,DSP.Sperm live rate,SLR.Abnormal sperm rate,ASR),the activities testicular mark enzymes and the levels of Sex hormones(testosterone,T,estradiol,E2) in testicular were measured.Results Compared with the control group,Fen cause the pathological changes of testicular tissue in rats,and the most serious injuries occurred in ZT 18.DSP,SLR,ACP and T in testicular were decreased,ASR and E2 were increased.Results from Cosinor analysis showed that Circadian rhythms of the changes compared to the control group in DSP,SLR and ACP were validated,and sensitive point in time to Fen was respectively at ZT 04,ZT 14,ZT 23.Conclusion The results suggested that the effects of Fen on male reproductive function were time-dependent in a circadian day.