预培汤对邻苯二甲酸二(2-乙基)己酯染毒大鼠胚胎发育及氧化应激的影响

Effect of Yupei Soup on Embryonic Development and Oxidative Stress in Rats Exposed to Di-2-ethylhexyl Phthalate

[目的]观察预培汤对邻苯二甲酸二(2-乙基)己酯(di-2-ethylhexyl phthalate,DEHP)染毒大鼠胚胎发育及氧化应激的影响。[方法]性成熟(70d龄)SD大鼠72只,雌雄各半,随机分为对照组、模型组、预培汤组,每组24只,雌雄各半。按照雌雄比例1:1合笼,确认妊娠后即开始造模。妊娠0d起,对照组予玉米油10mL·kg-1+0.9%氯化钠溶液10mL·kg-1,模型组予DEHP 500mg·kg-1+0.9%氯化钠溶液10mL·kg-1,预培汤组予DEHP 500mg·kg-1+预培汤10mL·kg-1,上、下午分别灌胃,持续至妊娠18d。至妊娠第19天处死孕鼠,剖腹取胎,称量胎鼠质量,记录各组活胎数、死胎数、畸形胎数;记录各组胎盘外观、色泽、质量情况,取胎盘组织行病理切片,观察不同组间胎盘形态学差异;检测胎盘组织总抗氧化能力(total antioxidant capacity,T-AOC)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、过氧化氢酶(catalase,CAT)、活性氧(reactive oxygen species,ROS)、丙二醛(malondialdehyde,MDA)水平。[结果]模型组大鼠孕中后期(10~18d)体重增加量明显低于对照组(P<0.05),胎鼠重量显著降低(P<0.05);预培汤组大鼠孕中后期(10~18d)体重增加优于模型组(P<0.05),且胎鼠重量较高(P<0.05)。病理学检查显示,模型组胎盘组织海绵滋养层明显疏松杂乱,出现较多空泡。预培汤组胎盘组织结构完整,层次明显清晰,迷路带、海绵滋养层、巨细胞滋养层均清晰可见,各层中细胞分布均优于模型组。胎盘组织氧化应激指标结果显示,模型组T-AOC、GSH-Px、SOD、CAT水平均显著低于对照组(P<0.01),ROS、MDA水平显著升高(P<0.01)。预培汤组TAOC、GSH-Px、SOD、CAT水平均高于模型组(P<0.05,P<0.01),ROS、MDA水平则明显降低(P<0.05)。[结论]预培汤可以减轻DEHP的胚胎生殖毒性,减少胎盘组织损伤,改善妊娠结局,其机制可能与纠正DEHP引起的胎盘组织内氧化应激失衡有关。

[Objective]To observe the effects of Yupei soup on embryonic development and oxidative stress in rats exposed to di-2-ethylhexyl phthalate(DEHP).[Methods]Seventy two SD rats of sexual maturity(70 days old),half male and female,were randomly divided into control group,model group and Yupei soup group,with 12 males and 12 females in each group.The mated ratio of male to female was 1:1,after pregnancy was confirmed,the rats were taken out and models were started to build.From pregnancy 0 d,control group was intragastric administrated with corn oil 10 mL·kg-1 and 0.9%sodium chloride solution 10 mL·kg-1,model group with DEHP 500 mg·kg-1 and 0.9%sodium chloride solution 10 mL·kg-1,Yupei soup group with DEHP 500 mg·kg-1 and Yupei soup 10 mL·kg-1,once in the morning and affternoon for each group,until pregnancy 18 d.The pregnant rats were sacrificed on pregnancy19 d.The fetuses were taken by caesarean section and the quality of the fetuses was weighed.The number of live births,the number of stillbirths,and the number of abnormal fetuses in each group were recorded.The appearance,color and quality of placenta were recorded.The placenta tissues were taken for pathological section,and the morphological differences of placenta between different groups were observed.The levels of total antioxidant capacity(TAOC),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),catalase(CAT),reactive oxygen species(ROS)and malondialdehyde(MDA)in placental tissue were detected.[Results]The weight gain of model group in the middle and late pregnancy(10~18 d)was significantly lower than that of control group(P<0.05),and the weight of the fetuses was significantly lower(P<0.05).The weight gain of Yupei soup group in the middle and late pregnancy(10~18 d)was higher than model group(P<0.05),and the weight of the fetus was higher(P<0.05).The results of pathological staining showed that the trophoblast of the placental tissue of model group was obviously loose and disordered,and more vacuoles appeared.The placenta of Yupei soup group had a complete structure and clear layers,the labyrinth zone,the sponge trophoblast and the giant cell trophoblast were clearly visible.The cell distribution in each layer was superior to model group.The results of placental tissue oxidative stress showed that the levels of T-AOC,GSH-Px,SOD and CAT in model group were significantly lower than those in control group(P<0.01),and the levels of ROS and MDA were significantly higher(P<0.01).The levels of T-AOC,GSH-Px,SOD and CAT in Yupei soup group were higher than those in model group(P<0.05,P<0.01),and the levels of ROS and MDA were significantly lower(P<0.05).[Conclusion]Yupei soup can alleviate embryonic reproductive toxicity of DEHP,reduce placental tissue damage and improve pregnancy outcome.The mechanism may be related to correcting the imbalance of oxidative stress in placental tissue caused by DEHP.