邻苯二甲酸二异丁酯对小鼠认知行为及海马神经细胞凋亡的影响

Effect of diisobutyl phthalate on learning and memory behavior and apoptosis of hippocampus cells in mice

目的初步研究邻苯二甲酸二异丁酯(DiBP)对小鼠被动回避学习记忆行为的影响,并探讨其是否可以通过血脑屏障并影响海马神经细胞凋亡。方法将60只昆明小鼠按体重随机分为5组,即对照组和4个不同剂量的DiBP剂量组(第Ⅰ组50mg/kg BW,第Ⅱ组250mg/kg BW,第Ⅲ组500mg/kg BW,第Ⅳ组1000mg/kg BW)。其中,对照组给予玉米油溶剂灌胃,而各剂量组给予相应剂量的邻苯二甲酸二异丁酯玉米油溶液灌胃,连续进行8周。实验结束后,分别对各组动物进行避暗箱行为学测试,测定脑组织中DiBP含量及海马神经细胞凋亡率,并在透射电镜下观察海马神经细胞超微结构。结果第Ⅳ组小鼠的被动回避能力显著性降低(P<0.05);第Ⅲ组和第Ⅳ组小鼠脑组织可检测出不同含量的DiBP,平均浓度分别为(1.27±0.56)和(1.96±0.42)μg/g;随着DiBP染毒剂量增高神经细胞凋亡率有升高的趋势,第Ⅳ组和对照组相比有显著性差异(P<0.05);各DiBP剂量组小鼠海马神经元的超微结构发生了不同程度的病理改变。结论在本试验条件下,高剂量DiBP可损伤实验小鼠被动回避学习记忆能力,并可穿透血脑屏障,增加海马神经细胞凋亡率,线粒体损伤是海马神经细胞凋亡规律改变的原因之一。

Objective To give the original research of diisobutyl phthalate （DiBP） on learning and memory behavior, determine whether it can through blood-brain barrier and effect apoptosis of hippocampus cells in mice. Methods Accommodating 60 Kunming mice to the animal house for 3 days, then dividing the mice into 5 groups according to their weights. That is, one control group and four experimental groups （ I group, 50mg/kg BW. 1/ group, 250mg/kg BW. III group, 500mg/kg BW. IV group, 1000mg/kg BW ）. The mice were fed with the corn oil in control group, and the other groups were fed with the related dose of diisobutyl phthalate mixture by gavages last for 8 weeks. At the end of dxperimental time, passive avoidance response was examined, then all of mice were killed, and choosed the brain tissues to test the DiBP content and apoptosis rate of hippoeampal cells and hippocampal uhrastructural alterations on electronmicroscopy. Results In the passive avoidance response test, the exposed animals of IV group showed learning impairment as compared to unexposed mice（P 〈 0.05）. DiBP was detected in m group and IV group, the mean content of them were （1.27 ± 0.56） and （ 1.96 ±0.42） Ixg/g. The apoptosis rate of hippocampal cells （ 1V group vs control group） increase significantly （P 〈 0.05）. Hippoeampal ultrastruetural were damaged in all dose- groups. Conclusion As a result, in the experiments, exposure to DiBP could exert passive avoidance neurobehavioral effects. DiBP could through blood-brain barrier after oral intake, and disordered the way of apoptosis of hippoeampal cells, and morphologic change of mitochondria mybe is the main reason of changes of neuron apoptosis.