氯乙烯亚慢性染毒对大鼠肝细胞周期及mir-21和mir-192表达的影响  

Effects of vinyl chloride monomer on cell cycle and expression of mir-21 and mir-192 in liver of rat

作　　者：梁洁[1] 胡君阳 高怡[1] 田凤洁[1] 吕懿[1] 仇玉兰[1] 

机构地区：[1]山西医科大学公共卫生学院卫生毒理学教研室,山西太原030001

出　　处：《中华疾病控制杂志》2016年第10期1057-1060,共4页Chinese Journal of Disease Control & Prevention

基　　金：山西省基础研究计划项目(2013011059-1)

摘　　要：目的探讨氯乙烯(vinyl chloride monomer,VCM)亚慢性染毒对大鼠肝细胞周期以及microRNA21(mir-21)和microRNA192(mir-192)表达量的影响。方法将32只健康斯普拉-道来(sprague dawley,SD)大鼠随机分为三个实验组(5 mg/kg组,25 mg/kg组和125 mg/kg组)与一个对照组(25 mg/kg清洁空气组),每组8只。采用腹腔注射进行VCM染毒,每周3次(隔日染毒)。染毒12周,处死大鼠并摘取肝组织。制备肝单细胞悬液,使用流式细胞技术检测G0/G1期、S期和G2/M期肝细胞所占百分比;提取肝细胞中的小片段RNA(<200 nt),采用实时荧光定量PCR技术检测大鼠肝细胞中mir-21和mir-192的表达量。结果 VCM染毒大鼠G0/G1期、S期和G2/M期肝细胞所占百分比在各剂量组间差异均无统计学意义(均有P>0.05);125 mg/kg组S期细胞与对照组相比明显增加,差异有统计学意义(t=-4.363,P=0.024)。各剂量组之间mir-21相对表达量差异有统计学意义(H=16.064,P=0.001);与对照组和5 mg/kg组相比,25 mg/kg组及125 mg/kg组mir-21相对表达量均降低,差异均有统计学意义(均有P<0.05)。各剂量组之间mir-192相对表达量差异有统计学意义(H=15.939,P=0.001);与对照组和5 mg/kg组相比,25 mg/kg组及125 mg/kg组mir-192相对表达量均降低,差异均有统计学意义(均有P<0.05)。结论 VCM亚慢性染毒导致大鼠肝细胞S期比例增加,mir-21和mir-192表达下调,具体调节机制有待进一步研究。Objective To explore the sub-chronic toxicity effects of vinyl chloride monomer （VCM） on cell cycle and the expression of cell cycle related microRNA 21 （mir-21） and microRNA 192 （mir-192） of rat liver. Methods Thirty-two healthy sprague dawley （SD） rats were randomly divided into three VCM exposure groups （5 mg/kg, 25 mg/kg and 125 mg/kg） and a control group （25 mg/kg clean air）. The rats were exposed by intraperitoneal injection three times a week （every other day） for three months. The flow cytometry was used to measure the percent of each phase（ GO/G1, S, and G2/M）. The mir-21 and mir-192 was extracted and then quantified using real-time fluorescent quantitative PCR. Resuits The percentage of each phase of cell cycle was not significantly different among four groups （ all P 〉 0. 05）. The proportion of S-phase cells in 125 mg/kg group was higher than the control group（t = -4. 363 ,P =0. 024）. Besides, the expressions of mir-21 varied significantly among four groups （H = 16. 064, P =0. 001 ） and, furthermore, decreased signif- icantly in both 25 mg/kg and 125 mg/kg group when they were compared with control and 5 mg/kg group （ all P 〈 0. 05 ）. Meanwhile, the expressions of mir-192 also varied significantly （H = 15. 939; P = 0. 001 ）, and decreased significantly in both 25 mg/kg and 125 mg/kg group, compared with control and 5 mg/kg group （all P 〈 0. 05 ）. Conclusions VCM subchronic exposure induced the increase of S-phase cells and decrease of the expression of mir-21 and mir-192.

关 键 词：氯乙烯 肝细胞 细胞周期 微RNAS 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学] R33[医药卫生—基础医学]