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

梁洁; 胡君阳; 高怡; 田凤洁; 吕懿; 仇玉兰

doi:10.16462/j.cnki.zhjbkz.2016.10.023

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

doi: 10.16462/j.cnki.zhjbkz.2016.10.023

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

基金项目:

山西省基础研究计划项目（2013011059-1）

详细信息

作者简介:
梁洁(1989-),女,山西平遥人,在读硕士研究生。主要研究方向:职业毒理学。

中图分类号: R329.2;R33;R996;R181
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出版历程
- 收稿日期: 2016-04-01
- 修回日期: 2016-07-21

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

Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China

摘要

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。
- 氯乙烯 /
- 肝细胞 /
- 细胞周期 /
- 微RNAs
Abstract: 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(G0/G1, S, and G2/M). The mir-21 and mir-192 was extracted and then quantified using real-time fluorescent quantitative PCR. Results 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 significantly 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 sub-chronic exposure induced the increase of S-phase cells and decrease of the expression of mir-21 and mir-192.
- Vinyl chloride /
- Hepatocytes /
- Cell cycle /
- MicroRNAs

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参考文献(23)

Laplanche A, Clavel F, Contassot JC, et al. Exposure to vinyl chloride monomer: report on a cohort study[J]. Br J Ind Med, 1987, 44(10): 711-715.

Brandt-Rauf PW, Li Y, Long C, et al. Plastics and carcinogenesis: The example of vinyl chloride[J]. J Carcinog, 2012,11:5.

Benada J, Macurek L. Targeting the Checkpoint to Kill Cancer Cells[J]. Biomolecules, 2015,5(3):1912-1937.

李武,贺庆芝,孙诗博,等. has-miR-16靶基因预测及生物信息学分析[J]. 中华疾病控制杂志, 2016,(2):193-197.

Yang J, Han S, Huang W, et al. A meta-analysis of microRNA expression in liver cancer[J]. PLoS One, 2014, 9(12): e114533.

Zhang Y, Wang X, Fu Y, et al. Expression profiling and pathway analysis of microRNA expression in the lungs of mice exposed to long-term, low-dose benzo(a)pyrene[J]. Molecular & Cellular Toxicology, 2014, 10(1): 67-74.

Izzotti A, Calin GA, Arrigo P, et al. Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke[J]. FASEB J, 2009,23(3):806-812.

陈桢坤,单云峰,何彬,等. miR-21在大鼠肝卵圆细胞活化和增殖过程中作用研究[J]. 中华肝脏病杂志, 2014,22(11):854-859.

Huang S, Deng Q, Feng J, et al. Polycyclic Aromatic Hydrocarbons-Associated MicroRNAs and Heart Rate Variability in Coke Oven Workers[J]. J Occup Environ Med, 2016, 58(1): e24-31.

王爱红, 朱守民, 周元陵, 等. 氯乙烯染毒大鼠代谢酶活性的动态变化和肝损伤[J]. 卫生研究, 2004, (3): 258-260.

Deng Q, Huang S, Zhang X, et al. Plasma microRNA expression and micronuclei frequency in workers exposed to polycyclic aromatic hydrocarbons[J]. Environ Health Perspect, 2014,122(7):719-725.

张盼红. 氯乙烯对大鼠肝细胞周期相关蛋白表达的影响[D]. 太原:山西医科大学, 2013.

Santo L, Siu KT, Raje N. Targeting Cyclin-Dependent Kinases and Cell Cycle Progression in Human Cancers[J]. Semin Oncol, 2015,42(6):788-800.

Morinello EJ, Ham AJ, Ranasinghe A, et al. Molecular dosimetry and repair of N(2),3-ethenoguanine in rats exposed to vinyl chloride[J]. Cancer Res, 2002,62(18):5189-5195.

王慧. 氯乙烯对HL-7702细胞周期的影响及G1/S关卡相关基因mRNA的表达[D]. 太原:山西医科大学, 2012.

刘庆成,杨淋清,陶功华,等. 低剂量甲醛对16HBE细胞的增殖促进及DNA损伤作用[J]. 中华疾病控制杂志, 2011,15(11):927-930.

席华星,聂继盛,牛侨. 苯并芘对神经细胞DNA损伤及细胞周期的影响[J]. 环境与职业医学, 2012,(10):620-623,628.

Gao S, Tian H, Guo Y, et al. miRNA oligonucleotide and sponge for miRNA-21 inhibition mediated by PEI-PLL in breast cancer therapy[J]. Acta Biomater, 2015, 25: 184-193.

Zhong Z, Dong Z, Yang L, et al. miR-21 induces cell cycle at S phase and modulates cell proliferation by down-regulating hMSH2 in lung cancer[J]. J Cancer Res Clin Oncol, 2012,138(10):1781-1788.

Sun J, Fan Z, Lu S, et al. miR-192 suppresses the tumorigenicity of prostate cancer cells by targeting and inhibiting nin one binding protein[J]. Int J Mol Med, 2016,37(2):485-492.

Jin Y, Lu J, Wen J, et al. Regulation of growth of human bladder cancer by miR-192[J]. Tumour Biol, 2015,36(5):3791-3797.

赵然,周鸣,王贺冉. MicroRNA参与肿瘤发生发展的调控机[J]. 中南大学学报(医学版), 2013, (12): 1282-1288.

Xue XY, Zhao B, Chao LM, et al. Interaction between two timing microRNAs controls trichome distribution in Arabidopsis[J]. PLoS Genet, 2014,10(4):e1004266.

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