妊娠期和妊娠哺乳期CdCl2暴露对子代小鼠海马损伤神经毒性影响OA

Objective:To investigate the neurotoxic effects of CdCl2 exposure during pregnancy and lactation on hippocampal injury in offspring mice.Methods:The pregnant mice were divided into 3 groups:the control group,the 5 mg/kg group and the 10 mg/kg CdCl2 group.The pregnant and lactating mice were respectively administered intragastrically with normal saline,5 mg/kg and 10 mg/kg of CdCl2.The birth status,physical development,histopathological changes and hippocampal cell apoptosis of offspring mice were observed.The brain organ coefficient was calculated.ICP-MS was used to evaluate the changes in cadmium,zinc and iron levels in the brain and blood of PDN1 and PDN30 offspring.qRT-PCR was used to analyze the expression of inflam-matory neurological function-related factors in the hippocampus of PND1 and PND30 offspring.Results:CdCl2 exposure during pregnancy and lactation had no effect on the body weight of PND1,PND30 offspring mice and maternal mice.The brain organ co-efficient of PND1 offspring in the 10 mg/kg group was reduced(P<0.01).CdCl2 exposure will lead to increased PND1 offspring's brain cadmium,and PND30 offspring's brain or blood cadmium,decreased iron and zinc levels(P<0.05).On the 2nd,3rd,4th and 5th days of positioning navigation,the escape latency of PND30 offspring in the 5 mg/kg and 10 mg/kg groups was prolonged compared to the control group(P<0.01);The spatial exploration test data showed that the times of the PND30 offspring in the 5 mg/kg and 10 mg/kg groups crossed the platform,and the target quadrant residence time was reduced(P<0.05).CdCl2 exposure caused different degrees of pathological changes in the CA1 and CA3 regions of the hippocampus of PND30 offspring mice,in-creased apoptosis in the CA1 and DG regions,and no pathological changes were found in the hippocampus of PND1 offspring.Compared to the control group,the mRNA of IL-1β,IL-6,TNF-α,APP,Tau,Ki67,BDNF,GFAP,Nestin,Arg-1,IL-4,and IL-10 in the 5mg/kg and 10mg/kg groups did not show statistically significant differences in the brain of the PND1 offspring(P>0.05);The mRNA expression of IL-1β,IL-6,TNF-α,APP,and Tau was upregulated in the 5 mg/kg or 10 mg/kg groups,and the expression of IL-4,IL-10,Arg-1,Ki67,BDNF,GFAP,and Nestin was downregulated in the hippocampus of the PND30 offspring mice(P<0.05).Conclusion:CdCl2 exposure during pregnancy or lactation proves that a small amount of CdCl2 enters the offspring through the placental glucocorticoid barrier and the blood-brain barrier,and most of it is transferred to the offspring through breast milk,which can cause reduced iron and zinc levels in PND1 and PND30 offspring,as well as damage to hippocampal memory and neurological function in PND30 offspring,and induce brain inflammatory response.