5-氮杂-2-脱氧胞苷对ADIH模型大鼠CYP2E1基因甲基化及蛋白表达的影响  

Effect of 5-azaza-2-deoxycytidine on the methylation level and protein expression of CYP2E1 gene in ADIH model rats

作　　者：胡宝翠 郝金奇[2] 侯瑞丽[2] 余艳琴[2] 张冬 周灏溦 王小红 吕博松 韦丽琴[2] HU Baocui;HAO Jinqi;HOU Ruili;YU Yanqin;ZHANG Dong;ZHOU Haowei;WANG Xiaohong;LYU Bosong;WEI Liqin(2017 graduate student, School of Public Health, Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014060, China;Department of Epidemiology and Health Statistics, Baotou Medical College, Inner Mongolia University of Science and Technology;2014 undergraduate of Public Health, Baotou Medical College, Inner Mongolia University of Science and Technology)

机构地区：[1]内蒙古科技大学包头医学院公共卫生学院,内蒙古包头014040 [2]内蒙古科技大学包头医学院流行病与卫生统计教研室 [3]内蒙古科技大学包头医学院公共卫生学院

出　　处：《包头医学院学报》2020年第1期36-39,42,共5页Journal of Baotou Medical College

基　　金：国家自然科学基金(81560540)。

摘　　要：目的:探讨5-氮杂-2-脱氧胞苷对抗结核药物致肝损伤大鼠CYP2E1基因甲基化水平和蛋白表达的影响,为临床抗结核药物致肝损伤的预防和治疗提供实验依据。方法:采用随机区组的方法将40只SPF级大鼠随机分成生理盐水组、单纯结核药组、5-氮杂-2-脱氧胞苷低剂量组(1 mg/kg)和5-氮杂-2-脱氧胞苷高剂量组(2 mg/kg),给药21 d。基于Mass Array平台检测CYP2E1基因启动子区甲基化水平,Western blot法检测CYP2E1的蛋白质表达水平。结果:CYP2E1基因甲基化水平在各组间差异无统计学意义(P>0.05)。5-氮杂-2-脱氧胞苷用药组大鼠肝湿重、肾脏系数、谷丙转氨酶(ALT)、总胆红素(TBil)、直接胆红素(DBiL)和CYP2E1的蛋白质表达水平低于单纯结核药组(P<0.05)。结论:5-氮杂-2-脱氧胞苷可通过下调CYP2E1蛋白表达量,达到改善肝功能的作用。Objective:To investigate the effects of 5-azaza-2-deoxycytidine on the methylation level and protein expression of CYP2E1 gene in rats with anti-tuberculosis drug-induced hepatic injury,so as to provide experimental basis for the prevention and treatment of liver injury caused by anti-tuberculosis drugs.Methods:Forty SPF rats were randomly divided into normal saline group,simple tuberculosis drug group,5-aziza-2-deoxycytidine low-dose group(1mg/kg)and 5-aziza-2-deoxycytidine high-dose group(2 mg/kg)for 21 days.Based on the Mass Array platform,the methylation level of CYP2E1 gene promoter region was detected,and the protein expression level of CYP2E1 was detected by Western blot.Results:There was no significant difference in the methylation level of CYP2E1 between groups(P>0.05).The liver wet weight,renal coefficient,ALT,TBiL,DBiL and CYP2E1 protein expression levels in the 5-azaza-2-deoxycytidine group were lower than those in the tuberculosis group(P<0.05).Conclusion:5-azaza-2-deoxycytidine can improve liver function by down-regulating the expression of CYP2E1 protein.

关 键 词：抗结核药物致肝损伤 5-氮杂-2-脱氧胞苷 CYP2E1 甲基化 蛋白表达 

分 类 号：R73[医药卫生—肿瘤]