亚慢性砷暴露对小鼠海马组织细胞凋亡的影响

Effect of subchronic exposure to arsenic on apoptosis of hippocampus cells in mice

目的观察亚慢性砷暴露致小鼠海马组织细胞凋亡作用,为探讨砷的神经毒性作用机制提供依据。方法昆明种小鼠40只,按体重将小鼠随机分为对照组、1 ppm、2 ppm和4 ppm三氧化二砷(As2O3)染毒组。通过自然饮用含不同浓度As2O3水的方式使小鼠砷暴露,连续染毒60 d。取海马组织,通过HE染色观察海马组织形态学变化,通过TUNEL和Hoechst双染以及透射电镜观察神经细胞凋亡。结果与对照组相比,染毒组小鼠的海马神经细胞出现肿胀,细胞核仁增多,细胞分布稀疏、排列紊乱。电镜下,可观察到染毒组小鼠的海马细胞出现膜皱缩,核仁消失,染色质凝聚、移动,分布于核周,进而裂解成几个碎片等凋亡细胞形态特征。TUNEL和Hoechst双染色分析结果显示,在染毒组小鼠海马切片可见凋亡染色阳性细胞,其凋亡指数显著高于对照组(P<0.01),且随着染毒剂量的增高而增多。结论亚慢性砷暴露可导致小鼠海马组织细胞凋亡。

Objective To examine the apoptosis of hippocampus cells in mice exposed to arsenic（As） subchronically and to provide evidences for exploring the mechanism of As-induced neurotoxicity.Methods Forty mice were divided into 4 groups of 10 each.Group 1 received drinking water alone（control）.Group 2,3 and 4 received 1 ppm,2 ppm and 4 ppm As2O3 respectively.As2O3 was given through drinking water.On the 60th day after As2O3 exposure,mice were decapitated and the hippocampus was taken.Pathomorphological changes of hippocampus tissue were observed by optical microscope.Apoptosis of hippocampus cells was also examined by electron microscopy and TUNEL-Hoechst.Results Compared with control,swelling of hippocampus cells,sparse of cell distribution and disorder of cell arrangement where foswhd.Under transmission electron microscopy,some neurons in mice exposed to As showed a shrunken cellular membrane,diminished cell body and increased delectron density of nuclear chromatin.The apoptosis indices of the hippocampal neuron in the mice exposed to As were significantly higher than those in controls（P0.01）.Conclusion The subchronic exposure to As may induce apoptosis of hippocampus cells in mice.