摘要
目的探讨淀粉样前体蛋白(APP)/早老素1(PS1)转基因小鼠脑皮质中过氧化物酶体增殖剂激活受体α(PPARα)的表达变化及意义。方法选择10只5月龄雄性APP/PS1双转基因C57BL/6J-TgN(APP/PS1)ZLFILAS小鼠为实验组,10只同遗传背景5月龄雄性C57BL/6J野生型小鼠为对照组。采用Morris水迷宫实验测定2组小鼠空间学习记忆能力,免疫组织化学法检测2组小鼠脑组织中β-淀粉样蛋白(Aβ)沉积情况,Western blot法检测2组小鼠脑皮质中PPARα、APP蛋白及肝组织中PPARα、脂酰辅酶A氧化酶1(ACOX1)及肉碱脂酰转移酶1(CPT1)蛋白表达,生物化学法检测2组小鼠血清中三酰甘油(TG)和总胆固醇(TC)水平。结果实验组小鼠不同时间点逃避潜伏期短于对照组,但2组间比较差异无统计学意义(P>0.05);实验组小鼠在目标象限游动时间短于对照组,但2组间比较差异无统计学意义(P>0.05)。对照组小鼠脑组织中未见到Aβ阳性斑块,实验组小鼠脑皮质和海马区可见大量大小不等的Aβ阳性斑块。实验组小鼠脑皮质中PPARα蛋白相对表达量显著低于对照组,APP蛋白相对表达量显著高于对照组(P<0.05)。实验组小鼠肝组织中PPARα、ACOX1、CPT1蛋白相对表达量显著高于对照组(P<0.05)。实验组小鼠血清TG水平显著高于对照组(P<0.05),实验组与对照组小鼠血清TC水平比较差异无统计学意义(P>0.05)。结论APP/PS1转基因小鼠存在脑组织和肝组织PPARα异常表达、脂质代谢紊乱,PPARα在阿尔茨海默病的发病机制中起重要作用。
Objective To investigate the expression and significance of peroxisome proliferator-activated receptor alpha(PPARα)in cerebral cortex of amyloid precursor protein(APP)/presenilin 1(PS1)transgenic mice.Methods Ten 5-month-old male APP/PS1 double-transgenic C57BL/6J-TgN(APP/PS1)ZLFILAS mice were selected as the experimental group,and ten 5-month-old male C57BL/6J wild-type mice with the same genetic background were selected as the control group.The spatial learning and memory ability of mice in the two groups was determined by Morris water maze,the deposition ofβ-amyloid(Aβ)in brain tissues of mice in the two groups was determined by immunohistochemistry,the expressions of PPARα,APP protein in cerebral cortex and PPARα,fatty acyl-CoA oxidase 1(ACOX1),carnitine fatty acyltransferase 1(CPT1)in liver tissues of mice in the two groups were determined by Western blot,and the levels of serum triglyceride(TG)and total cholesterol(TC)of mice in the two groups were detected by biochemical method.Results The escape latency of mice in the experimental group was shorter than that in the control group at different time points,but there was no significant difference in the escape latency of mice between the two groups(P>0.05).The swimming time in the target quadrant of mice in the experimental group was shorter than that in the control group,but there was no significant difference in the swimming time of mice between the two groups(P>0.05).Aβ-positive plaque was not found in the brain tissue of mice in the control group,while a large number of Aβ-positive plaques with varying sizes were found in the cerebral cortex and hippocampus of mice in the experimental group.The relative expression level of PPARαprotein in the cerebral cortex in the experimental group was significantly lower than that in the control group,and the relative expression level of APP protein was significantly higher than that in the control group(P<0.05).The relative expression levels of PPARα,ACOX1 and CPT1 protein in the liver tissue of mice in the experimental group were significantly higher than those in the control group(P<0.05).The level of serum TG of mice in the experimental group was significantly higher than that in the control group(P<0.05),and there was no significant difference in the level of serum TC of mice between the experimental group and the control group(P>0.05).Conclusion APP/PS1 transgenic mice have abnormal expression of PPARαin brain and liver tissues and disorder of lipid metabolism,PPARαmay play an important role in the pathogenesis of Alzheimer′s disease.
作者
张李娟
赵舒祥
王若溪
卜勇军
杨磊
原志庆
李文强
石如玲
ZHANG Lijuan;ZHAO Shuxiang;WANG Ruoxi;BU Yongjun;YANG Lei;YUAN Zhiqing;LI Wenqiang;SHI Ruling(School of Public Health,Xinxiang Medical University,Xinxiang 453003,Henan Province,China;School of Nursing,Xinxiang Medical University,Xinxiang 453003,Henan Province,China;Basic Medical College,Xinxiang Medical University,Xinxiang 453003,Henan Province,China;Henan Key Laboratory of Biological Psychiatry,Xinxiang 453002,Henan Province,China)
出处
《新乡医学院学报》
CAS
2022年第9期801-805,共5页
Journal of Xinxiang Medical University
基金
河南省科技攻关计划项目(编号:202102310404)
新乡市科技攻关计划项目(编号:GG2019006)
河南省生物精神病学重点实验室开放课题(编号:ZDSYS2019004)。
