氯化锂对APP/PS1双转基因小鼠脑组织中β淀粉样蛋白含量的影响

Lithium Chloride Treatment Reduces the Content of β-Amyloid Peptide in Brain Tissues of APP/PS1 Double Transgenic Mice

目的:探究氯化锂(LiCl)对APP/PS1双转基因小鼠脑组织中β-淀粉样肽(Aβ)含量的影响。方法:用PCR及琼脂糖电泳方法分选4月及8月龄野生型及APP/PS1双转基因小鼠,将小鼠分为野生型(WT)组、WT+Li组、APP/PS1组及APP/PS1+Li组4组(n=6),WT+Li组和APP/PS1+Li组小鼠采用LiCl灌胃2个月[100mg/(kg·d)],WT组及APP/PS1组采用等量生理盐水灌胃处理(试验检测时4组小鼠为6月及10月龄);采用免疫组织化学法检测6月及10月龄小鼠脑组织中老年斑数量,采用ELISA法测定小鼠脑组织内不可溶性Aβ含量。结果:灌胃结束时,与WT组小鼠比较,APP/PS1双转基因小鼠脑组织内老年斑数量、不可溶性Aβ含量均显著升高(P<0.05),10月龄小鼠更明显;与APP/PS1组小鼠比较,APP/PS1+Li组小鼠脑组织内老年斑数量及不可溶性Aβ含量显著降低,差异有统计学意义(P<0.05)。结论:LiCl可减少APP/PS1双转基因小鼠脑组织Aβ含量,这可能是其治疗精神性疾病的机制之一。

Objective:To investigate the effect of lithium chloride(LiCl)on the content ofβ-amyloid peptide(Aβ)in the brains of APP/PS1 double transgenic mice.Methods:Wild-type(WT)and APP/PS1 double transgenic mice at 4 and 8 months old were verified by genotyping.Experimental groups included WT group,WT+Li group,APP/PS1 group and APP/PS1+Li group.WT+Li group and APP/PS1+Li group were intragastrically administered with 100 mg/(kg·d)LiCl for 2 months,while WT group and APP/The PS1 group was treated with the same amount of normal saline.Senile plaques in the brain tissues of mice at 6 and 10 months old were detected by immunohistochemistry.The content of insoluble Aβin mouse brain tissue was determined by ELISA.Results:At the end of the treatment,,the numbers of senile plaques and insoluble Aβin APP/PS1 double transgenic mice were significantly increased when compared with WT group(P<0.05).Senile plaques and insoluble Aβwere more obvious in 10 months-old mice.Compared with APP/PS1 group,the number of senile plaques and the content of insoluble Aβwere significantly decreased in the brains of APP/PS1+Li group(P<0.05).Conclusion:LiCl treatment can reduce the Aβcontent in brain tissue of APP/PS1 double transgenic mice.It may be one of the mechanisms used in clinical treatment of mental diseases.