生命早期低剂量镉暴露对阿尔茨海默病模型小鼠肝脏功能及脂质代谢的影响OA

OBJECTIVE:To investigate effect of low-dose cadmium exposure in early life on liver function and lipid metabolism in a mouse model for Alzheimer's disease(AD mice).METHODS:AD and wild-type(WT)mice were exposed to cadmium via drinking water(0,1,and 10 mg/L)from one week before pregnancy until 6 months of age.Blood samples were collected from F1 generation mice at the ages of 1,3,and 6 months,and serum lipid and liver function indices were measured.Liver tissues were collected,and mRNA expression levels of metallothionein 1(MT1)and metallothionein 2(MT2)in the livers were determined by quantitative real-time polymerase chain reaction(RT-qPCR).RESULTS:Compared with 3-month-old toxicant-exposed WT mice,age-and dose-matched AD mice showed increased body weight,liver weight,liver coefficient,TC,TG,HDL,and ALT(P＜0.05),along with decreased LDL,AI,and hepatic MT1 mRNA expression(P＜0.05).In comparison with 6-month-old toxicant-exposed WT mice,age-and dose-matched AD mice exhibited elevated body weight,liver weight,TC,TG,and HDL(P＜0.05),along with decreased AST and AST/ALT ratio(P＜0.05).Furthermore,interactive effects of cadmium and APP/PS1 genotype were observed on body weight,liver weight,TC,LDL,and TG/HDL ratio(P＜0.05).CONCLUSION:Low-dose cadmium exposure in early life can induce dyslipidemia and abnormal liver function in AD mice,therefore exposure to environmental cadmium levels(1 mg/L)can reduce expression level of MT1 and MT2.