丙烯酰胺生殖毒性和发育毒性效应性生物标志物研究

目的：研究丙烯酰胺对机体造成的生殖毒性和发育毒性,并找出丙烯酰胺生殖毒性和发育毒性的效应性生物标志物。方法：通过对SD雄鼠灌胃22.5、11.25、5.625mg/（kg·d）的丙烯酰胺溶液,分析对其睾丸和附睾的影响,还对精子畸形率和睾丸内抗氧化酶系统进行评价,通过研究丙烯酰胺在动物模型中产生的效应性生物标志物来评价其生殖毒性。采用饮水给予怀孕第6d的孕鼠20.0、10.0、5.0mg/（kg·d）的丙烯酰胺,在怀孕0、7、12、16、20d称量体重并每天监测其饮水消耗量,观察胎鼠身长、尾长和骨骼发育情况;对断乳后的幼鼠采用直接饮水接触丙烯酰胺,在3—6w每周处死部分幼鼠,对其脏器和血液进行分析,通过研究丙烯酰胺在动物模型中产生的效应性生物标志物来评价其发育毒性。结果：丙烯酰胺显著增加了SD大鼠精子畸形率,显著降低了SD大鼠睾丸内抗氧化酶的活性;同时,丙烯酰胺导致幼鼠尾长的发育异常,幼鼠的肝、肾、脾、甲状腺发生组织病变,骨骼畸形率显著增加。结论：精子畸形率、睾丸内抗氧化物酶能够反应丙烯酰胺的生殖毒性,可作为丙烯酰胺生殖毒性的效应生物标志物;幼鼠尾长、骨骼畸形、组织病理学改变可反应丙烯酰胺的发育毒性,可作为丙烯酰胺的发育毒性的效应生物标志物。

Research on Biomarkers of Effect of Reproductive and Developmental Toxicity of Acrylamide

【Objective】The reproductive and developmental toxicity of acrylamide were mainly researched,and the biomarkers of reproductive toxicity and developmental toxicity were detected.【Method】Sprague-Dawley male rats were given acrylamide with 22.5,11.25,5.625 mg/（kg·d） to analyze the effect on the testis and epididymis.Sperm deformity rate and antioxidant enzyme system were evaluated,and the biomarkers in animal model were measured to evaluate the reproductive toxicity of acrylamide.Pregnant Sprague-Dawley dams were given acrylamide at 20.0,10.0,5.0 mg/（kg·d） in the drinking water beginning on gestational day 6.Body weight and water intake were measured beginning on gestational day（GD） 0,7,12,16,20 d.The developmental state of body length,tail length and bone of fetal rats were observed.Pups were given acrylamide in the drinking water directly after weaning,some fetal rats were executed every week from 3to 6 weeks,the organ tissues and blood were analyzed,and the biomarkers in animal model were measured to evaluate the developmental toxicity of acrylamide.【Result】Acrylamide significantly increased sperm deformity and decreased the activity of antioxidant enzymes.Acrylamide led to the developmental abnormalities of tail length and tissue lesions of liver,kidney,spleen,thyroid and increased the skeletal malformations significantly.【Conclusion!!】Sperm deformity and antioxidant enzymes could be used as biomarkers of reproductive toxicity,and tail length,skeletal dysplasia and pathological changes of organs could be used as biomarkers of developmental toxicity.