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P300-PPAR-γ通路在孕期胎儿酒精综合征小鼠子代神经细胞糖代谢紊乱中的作用
胡文广,刘平,陈聪,李思秀
0
(成都市妇女儿童中心医院儿童神经内科;成都市第一人民医院儿科)
摘要:
【摘要】 目的 探讨P300-PPAR-γ通路在孕期胎儿酒精综合征(FAS)小鼠子代神经细胞糖代谢紊乱中的机制。方法 选取雌性c57小鼠妊娠期给予酒精灌胃(5 μL/g·d 50%乙醇)建立孕期酒精综合征模型为酒精组,另设对照组(予生理盐水灌胃)。分娩后子代饲养至8周,进行Morris水迷宫、跳台实验评估小鼠神经行为。利用二氧化碳窒息处死子代实验小鼠,剖开颅腔后分离大脑组织,用于后续实验。qPCR检测p300、GCN5的表达水平,qPCR及Western blot检测PPAR-γ、GLUT-1的表达水平,ChIP结合qPCR检测p300与PPAR-γ启动子结合水平。结果 酒精组子代小鼠学习记忆能力较对照组下降(P<0.05),酒精组子代小鼠脑组织中p300、PPAR-γ及GLUT-1表达较对照组降低(P<0.05),GCN5表达两组间比较差异无统计学意义(P>0.05)。酒精组子代p300与PPAR-γ启动子结合水平较对照组明显下降(P<0.05)。 结论 FAS子代小鼠中p300介导组蛋白乙酰化修饰下调PPAR-γ表达,引起脑组织糖代谢异常。
关键词:  孕期酒精综合征  子代小鼠  p300  PPAR-γ  糖代谢紊乱
DOI:
基金项目:四川省卫生和计生委科研课题
Role of p300-PPAR-γ pathway in neurocyte glucose metabolism disorder in FAS offspring mice
HU Wenguang,LIU Ping,CHEN Cong,LI Sixiu
(Department of Pediatrics Neurology, Chengdu Women′s & Children′s Central Hospital;Department of Pediatrics, Chengdu First People′s Hospital)
Abstract:
【Abstract】 Objective To investigate the effect of fetal alcohol syndrome (FAS) on glucose metabolism in the offspring mice and underlying mechanisms. Methods Wild type female mice were exposed with alcohol at 5ul/g/d (50% concentration) during gestation to establish FAS model. Normal saline was used as control. F1 offspring mice were fed for 8 weeks after birth. The water maze test and stepdown test were used to detect learning and memory ability of F1 mice. The mRNA levels of P300, and GCN5 were detected by qPCR. The expression of PPAR-γ and GLUT-1 at mRNA and protein levels were determined by qPCR and Western blotting. ChIPqPCR was employed to analyze the binding status of p300 with the promoter region of PPARγ. Results Learning ability and memory in the offspring mice were declined significantly (P<0.05). The expression levels of p300, PPARγ and GLUT1 were decreased compared with the controls (P<0.05). Binding affinity of p300 with the promoter of PPAR-γ was reduced (P<0.05). Conclusion P300 regulating PPAR-γ low expression may cause glucose metabolism disorder of the neurocytes in FAS offspring mice.
Key words:  Fetal alcohol syndrome  Offspring mice  p300  PPAR-γ  Glucose metabolism disorder

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