microRNA-125b在孕期酒精暴露所致新生小鼠脑神经元凋亡中的作用  

Role of miR125b in alcohol exposure during gestation caused neuron apoptosis in newborn mice

作　　者：胡文广 赵力立 邓佳 毛丹丹 李思秀 HU Wen-guang;ZHAO Li-li;DENG Jia;MAO Dan-dan;LI Si-xiu(Department of Pediatrics Neurology,Chengdu Women's&Children's Central Hospital,Chengdu 610091,Sichuan,China)

机构地区：[1]成都市妇女儿童中心医院儿童神经内科,四川成都610091

出　　处：《广东医学》2021年第5期530-533,共4页Guangdong Medical Journal

基　　金：四川省卫生和计生委科研课题(18PJ043)。

摘　　要：目的探讨microRNA-125b(miR125b)调控孕期酒精暴露致胚胎神经元细胞凋亡的可能机制。方法给予孕期小鼠持续连续酒精暴露[50%酒精,5μL/(g·d)],对照组予以0.9%NaCl暴露;检测出生小鼠脑/体重比;Tunnel法检测新生小鼠脑组织中神经元细胞凋亡情况;利用定量PCR检测miR125b、p53、凋亡基因Bax mRNA表达水平,利用Western blot检测p53及Bax蛋白表达;体外情况下给予鼠PC-12细胞酒精暴露,然后进行miR125b mimic转染以上调miR125b表达;再次检测miR125b、p53及Bax表达水平。结果与对照组相比,酒精暴露组小鼠出生脑/体重比显著降低(P<0.05),脑组织中神经元细胞凋亡增加。酒精暴露组新生小鼠脑组织中miR125b表达明显降低,而p53及Bax在mRNA和蛋白水平均显著升高(P<0.05);PC-12细胞转染miR125b-mimic使其过表达后,miR125b表达显著升高,与酒精暴露组相比p53及Bax表达明显下降(P<0.05)。结论miR125b通过影响p53通路进而参与影响孕期酒精暴露致小鼠脑神经元凋亡。Objective To investigate the role of miR125b in alcohol utero exposure induced neuron apoptosis.Methods Pregnant mice were exposed to alcohol(50%5μL/g/d)during the whole gestation and assigned as exposed group;while mice of control group were exposed to normal saline.Brain/birth weights ratio were detected.Tunnel method was applied for assessment of neuron apoptosis;and mRNA levels of miR125b,p53 and apoptosis related gene Bax were measured by Q-PCR methods.Western blot was used to detect protein levels of p53 and Bax.In vitro,PC-12 cells were exposed to ethanol,and miR125b mimic was transfected to PC-12 cells to up-regulate miR125b;and miR125b,p53 and Bax expression levels were detected.Results Brain/birth weight ratio of newborn mice in alcohol exposed group were significantly lower than those in control group(P<0.05).Neuron apoptosis level was increased in exposed group.miR125b expression was significantly reduced in exposed group;p53 and Bax were significantly increased both in mRNA and protein levels in exposed groups,compared to control group(P<0.05).miR125b mimic transfection induced over-expression of miR125b(P<0.05);thus p53 and Bax significantly decreased both in mRNA and protein levels after miR125b up-regulation after ethanol exposure(P<0.05).Conclusion Alcohol exposure during gestation may cause neuron apoptosis through decrease of miR125b,which might negative regulate p53.

关 键 词：胎儿酒精综合征 miR125b P53 细胞凋亡 

分 类 号：R741.02[医药卫生—神经病学与精神病学] R363.2[医药卫生—临床医学]