氯乙烯对肝细胞周期G_1/S关卡相关蛋白表达影响  

Influence of vinyl chloride monomer on G_1/ S checkpoint and related protein expression in hepatocytes

作　　者：胡君阳 李阳[1] 王慧[1] 张文平[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：《中国公共卫生》2016年第2期191-194,共4页Chinese Journal of Public Health

基　　金：中国博士后科学基金(20100471583);山西省基础研究计划项目(2013011059-1)

摘　　要：目的探讨氯乙烯(VCM)对细胞周期G1/S关卡功能影响及可能的机制。方法将人正常肝细胞HL-7702暴露于VCM气体(体积分数为0.8%、2.5%、7.5%、15.0%和30.0%)和空气(对照组)48 h后用流式细胞仪检测HL-7702细胞周期;Western blot测定细胞中G1/S关卡相关蛋白表达水平。结果染毒48 h后,在<7.5%剂量时,HL-7702细胞G0/G1期细胞百分数随染毒剂量增加呈上升趋势,与对照组[(73.35±1.56)%]比较,7.5%剂量组G0/G1期细胞百分比[(78.52±4.46)%]升高,差异有统计学意义(P<0.01);与对照组[(12.85±0.02)%]比较,2.5%剂量组S期细胞百分比[(10.97±0.17)%]下降,差异有统计学意义(P<0.05);细胞周期蛋白依赖性激酶(CDK 4)和P16蛋白表达量均呈上升趋势,与对照组比较,7.5%剂量组HL-7702细胞CDK 4、P16表达[分别为(1.43±0.51)、(0.80±0.30)]均升高,差异均有统计学意义(均P<0.05)。结论低剂量VCM染毒可使肝细胞发生G1期阻滞,高剂量时G1期阻滞作用消失;其机制主要与上调P16、CDK 4蛋白表达有关。Objective To explore the impact of vinyl chloride monomer（ VCM） on G1/ S checkpoints in hepatocytes and its mechanisms. Methods Human normal liver cells（ HL-7702） were exposed to gaseous VCMat concentrations of 0. 8%,2. 5%,7. 5%,15%,and 30%（ volume fraction） and normal air（ control group） for 48 hours. The fraction of cell cycle of HL-7702 was detected with flowcytometry; the expression levels of relevant proteins were detected with Western blot. Results After exposed to VCMlower than 7. 5% for 48 hours,the ratio of the cells at G0/ G1 phase increased with the increment of VCMconcentration,and the proportion of 7. 5% VCMexposed cells at G0/ G1 phase was significantly higher than that of the control cells（ 78. 52 ± 4. 46% vs. 73. 35 ± 1. 56%,P〈0. 01）; whereas the proportion S phase for the cells exposed to 2. 5% VCMdecreased significantly compared to that of the control cells（ 10. 97 ± 0. 17%vs. 12. 85 ± 0. 02%,P〈0. 05）. The expressions of cyclin dependent kinase 4（ CDK4） and P16 protein increased significantly in the cells exposed to 7. 5% VCMcompared with the control cells（ all P〈0. 05）. Conclusion Low-dose VCMexposure could induce G1 phase arrest in human hepatocytes and the effect may be mainly related to the decreased P16 expression and increased CDK4 expression.

关 键 词：氯乙烯(VCM) G1/S关卡 P16 细胞周期蛋白(cyclin D1) 细胞周期蛋白依赖性激酶(CDK 4) 

分 类 号：R994.2[医药卫生—毒理学]