维生素B_(12)缺乏对人肝细胞增殖、凋亡和染色体不稳定性的影响  

EFFECTS OF VITAMIN B_(12) DEFICIENCY ON PROLIFERATION,APOPTOSIS AND CHROMOSOMAL INSTABILITY IN HUMAN HEPATOCYTES IN VITRO

作　　者：王晗[1,2] 刘桥刚 周滔[1,2] 倪娟[1,2] 汪旭[1,4] WANG Han;LIU Qiao-gang;ZHOU Tao;NI Juan;WANG Xu(School of Life Science,Yunnan Normal University,Kunming 650500;Engineering Research Center of Sustainable Development and Utilization of Biomass Energy,Ministry of Education,Kunming 650500;School of Chemical Biology and Environment,Yuxi Normal University,Yuxi 653100;Yeda Institute of Gene and Cell Therapy,Taizhou 318000,China)

机构地区：[1]云南师范大学生命科学学院,昆明650500 [2]云南师范大学,生物能源持续开发与利用教育部工程研究中心,昆明650500 [3]玉溪师范学院化学生物与环境学院,玉溪653100 [4]台州耶大基因与细胞治疗研究院,台州318000

出　　处：《营养学报》2023年第1期57-62,共6页Acta Nutrimenta Sinica

基　　金：国家自然科学基金(No.31860301);云南省基础研究计划项目(No.202101AU070047);云南师范大学博士启动基金项目(No.2019ynnuPhdwh)。

摘　　要：目的探讨两种形式的维生素B_(12),氰钴胺(cyancobalamin,CNCbl)和甲钴胺(methylcobalamin,MeCbl)缺乏对人肝细胞增殖、凋亡和染色体不稳定性(chromosomal instability,CIN)的影响。方法配制含CNCbl或MeCbl浓度为37(缺乏)、370、3700(充足)pmol/L的RPMI-1640干预培养液,培养人肝L-02细胞和QGY细胞9d,胞质分裂阻断微核细胞组试验(cytokinesis-blockmicronucleuscytomeassay,CBMN-Cyt)评价受试细胞核分裂指数(nuclear division index,NDI)、CIN和细胞凋亡水平。结果与VB_(12)为3700 pmol/L培养条件相比,370 pmol/L的CNCbl和MeCbl对L-02和QGY细胞CIN和细胞凋亡率无显著影响,而37pmol/L的CNCbl和MeCbl均显著降低二株细胞的NDI水平(P<0.05),诱导二株细胞CIN升高(P<0.05)和凋亡发生(P<0.05);在VB_(12)缺乏和充足条件下,与MeCbl相比,CNCbl诱导受试细胞NDI显著降低(P<0.05),CIN和细胞凋亡率显著升高(P<0.05)。结论二种形式的VB_(12)缺乏均可诱导人肝细胞染色体不稳定并降低细胞分裂能力,引起细胞凋亡;与CNCbl相比,MeCbl在维持细胞增殖状态、基因组稳定及细胞凋亡过程中更为有效。Objective To investigate the effects of vitamin B_(12)deficiency(including cyancobalamin(CNCbl)and methylcobalamin(MeCbl))on the proliferation,apoptosis and chromosomal instability(CIN)of human hepatocytes.Methods Human hepatocytes L-02 and hepatoma cells QGY were cultured in RPMI-1640 medium containing CNCbl at concentrations of 37(deficient),370 and 3700(sufficient)pmol/L or MeCb,respectively for 9 days.The nuclear division index(NDI),CIN and apoptosis levels were evaluated by cytokinesis-block micronucleus cytome assay(CBMN-Cyt).Results Compared with the vitamin B_(12)at 3700 pmol/L,CNCbl and MeCbl at 370 pmol/L had no significant effects on CIN and apoptosis rate in L-02 and QGY cells,while CNCbl and MeCbl at 37 pmol/L significantly decreased the NDI level(P<0.05),increased CIN(P<0.05)and apoptosis rate(P<0.05)in two test cells.CNCbl induced a significant decrease in NDI(P<0.05),and a significant increase in CIN(P<0.05)and apoptotic rate(P<0.05)compared with MeCbl in the deficient(37 pmol/L)or sufficient(3700 pmol/L)conditions in L-02 and QGY cells.Conclusion Vitamin B_(12)deficiency,either MeCbl or CNCbl,can induce CIN,reduce cell division ability,and cause apoptosis in human hepatocytes.Compared with CNCbl,MeCbl is more effective in maintaining cell proliferation,genome stability and apoptosis.[ACTA NUTRIMENTA SINICA,2023,45(1):57-62]

关 键 词：氰钴胺 甲钴胺 核分裂指数 染色体不稳定性 细胞凋亡 

分 类 号：Q291[生物学—细胞生物学]