摘要
目的探索生命早期补充维生素B_(12)对海马神经元细胞(HNCs)DNA甲基化水平及抗β淀粉样蛋白(Aβ)毒性的作用及机制。方法新生大鼠出生12 h内取HNCs体外培养,随机分为空白组、模型组及维生素B_(12)低、中、高剂量组,进行不同剂量维生素B_(12)干预,HPLC法测定DNA甲基化水平,同时观察生命早期维生素B_(12)干预对成熟期HNCs细胞Aβ1-42染毒后细胞增殖率、细胞凋亡率、丙二醛含量、超氧化物歧化酶(SOD)活力和谷胱甘肽过氧化物酶(GSH-PX)活力的影响。结果维生素B_(12)早期干预HNCs细胞DNA甲基化水平较空白组明显降低,差异有统计学意义(P<0.05);Aβ染毒可造成HNCs细胞增殖率显著下降、细胞凋亡率明显升高、丙二醛含量增高、SOD活力和GSH-PX活力降低,差异有统计学意义(P<0.05)。与模型组比较,生命早期补充维生素B_(12)可提高成熟期HNCs细胞Aβ染毒后的细胞增殖率,降低细胞凋亡率,减少丙二醛含量,增加SOD和GSH-PX活力,差异有统计学意义(P<0.05)。结论维生素B_(12)生命早期干预,有助于降低神经元细胞的甲基化水平,并在成熟期神经元细胞发挥对抗Aβ神经毒性作用,参与神经元细胞氧化应激,促进细胞增殖,减缓神经细胞凋亡。
Objective To explore the effect of vitamin B_(12)supplementation in early life on DNA methylation level and Aβtoxicity in hippocampal neuron cells(HNCs)and its mechanism.Methods HNCs in 12 h of birth of the newborn rats were taken for culture in vitro,which were randomly divided into 5 groups:blank group,model group,low-dosage vitamin B_(12)group,medium-dosage group and high-dosage group.Different dosages of vitamin B_(12)were given for intervention.HPLC method was used to determine the level of DNA methylation;meanwhile,observe the effect of early intervention by vitamin B_(12)on proliferation rate(PR)and apoptosis rate(AR)of mature HNCs after Aβ1-42 toxification,MDA content,SOD activity and GSH-PX activity.Results The DNA methylation level of HNCs intervened by vitamin B_(12)at early stage was significantly lower than the control group(P<0.05);Aβtoxification could significantly decrease the PR and increase the AR of HNCs,and increase MDA content and reduce the activity of SOD and GSH-PX(P<0.05).Compared with model group,vitamin B_(12)supplementation in early life could increase PR of mature HNCs after Aβtoxification,decrease the AR,reduce MDA content,and increase the activity of SOD and GSH-PX,the difference being statistical(P<0.05).Conclusion Supplementation of vitamin B_(12)in early life is helpful to decrease the methylation level of neuron cells,which plays an anti-Aβneurotoxicity role in mature neuron cells,participates in oxidative stress of neuron cells,promotes cell proliferation and slows down apoptosis of neuron cells.
作者
刘乃榕
李景辉
任刚
李晶
詹杰
LIU Nairong;LI Jinghui;REN Gang;LI Jing;ZHAN Jie(Liaoning Vocational College of Medicine,Shenyang 110000,China)
出处
《中国中西医结合儿科学》
2021年第2期99-103,共5页
Chinese Pediatrics of Integrated Traditional and Western Medicine
基金
辽宁省科学事业公益研究基金计划项目(20170032)。