脱氧雪腐镰刀菌烯醇对小鼠的胚胎毒性和致畸作用

Embryotoxic and Teratogenic Effects of Deoxynivalenol on Mice

目的研究脱氧雪腐镰刀菌烯醇(deoxynivalenol,DON)致小鼠胚胎毒性和致畸作用。方法将34只健康妊娠SPF级昆明小鼠随机分为空白对照(不做任何处理)组、溶剂对照(30%丙二醇)组和低(4 mg/kg)、中(6.4 mg/kg)组,每组6只小鼠,高(10 mg/kg)剂量DON染毒组10只小鼠。小鼠于孕期第7～10天连续进行腹腔注射染毒,染毒容量分别为11.4、18.3、28.6 ml/kg。于妊娠第18天处死孕鼠,记录活胎数、吸收(死)胎数、胎鼠体重。肉眼观察有无畸形;采用阿尔新蓝和茜素红进行活胎鼠骨骼、软骨双重染色,镜下观察骨骼发育情况。结果与溶剂对照组比较,高、中、低剂量DON染毒组活胎数、产仔数和胎鼠体重均较低,差异有统计学意义(P<0.05);而吸收胎数均较高,但差异无统计学意义。随着DON染毒剂量的升高,活胎数、产仔数和胎鼠体重呈下降趋势,吸收胎数呈上升趋势。高剂量DON染毒组胎鼠出现尾部畸形(包括短尾、卷尾、短尾合并卷尾),发生率为58.06%(18/31)。各DON染毒组均不同程度地出现骨骼畸形,以中轴骨骼畸形为主,伴随四肢畸形。高剂量DON染毒组31只胎鼠均出现多发性骨骼畸形,且常出现多种畸形并存,以胸骨及肋骨畸形最为常见,其肋骨缺失率高达96%。空白对照组仅出现一例肢体(六趾)畸形,溶剂对照组未出现任何畸形。结论高剂量(10 mg/kg)DON对小鼠具有明显的胚胎毒性和致畸作用,可导致小鼠多发性骨骼畸形。

Objective To investigate the embryotoxic and teratogenic effects of deoxynivalenol（DON） on mice.Methods Pregnant mice were divided into three groups：solvent group,control group and DON test group.Pregnant mice in DON test group were given DON by intraperitoneal injection at the doses of 4,6.4 and 10 mg/kg at 7th-10th day of gestation.DON doses were 11.4,18.3,28.6 ml/kg respectively.Pregnant mice in solvent group were injected with 30% propylene glycol and mice in the control group were left untreated.The body weight of fetal rats and the number of fetal and alive were recorded,deformations visible to the naked eye were observe and examined when mice were sacrificed at the 18th day of gestation.The fetus skeletal development and abnormality were observed by alcian blue and alizarin red skeletal staining.Results Statistically significant differences were observed between DON treated mice and normal controls in birth weight and the average litters（P0.05）;Varying degrees of skeletal abnormality was observed in all DON treated groups.The most common malformations were skeleton abnormality and usually with limp abnormality.Multiple skeletal malformations were examined in 31 pregnant mice of 10 mg/kg DON treated group.Sternum and ribs abnormality was the most common,malformation rate of the ribs was more than 96%.No malformations were observed in solvent group.Only one limp deformity was found in normal control group.Conclusion DON has obvious toxic and teratogenic effects on the embryos of mice and may induce multiple skeletal deformities.