低浓度苯暴露与外周血淋巴细胞miR-223和miR-155表达的关联研究

Effect of exposure to low concentrations of benzene on miR-223 and miR-155 expression in peripheral blood lymphocytes

目的分析低浓度苯暴露对职业人群外周血淋巴细胞miRNA155(miR-155)和miRNA223(miR-223)表达的影响。方法选择浙江省宁波市2家小型金属制品企业、1家中型化学原料和化学制品制造企业苯职业暴露的男性员工100人纳入苯暴露组,选择年龄匹配、无苯职业暴露的男性员工60人纳入未暴露组;通过问卷调查收集年龄、体质指数(BMI)、吸烟、饮酒、疾病史、用药史和血常规等资料。采用热解吸-气相色谱法检测工作场所苯8小时时间加权平均浓度(C_(TWA)),采用高效液相色谱-串联质谱法检测尿8-羟基脱氧鸟苷(8-OHdG),采用荧光定量反转录PCR测定miR-155和miR-223的表达量。采用多因素logistic回归模型分析miR-155和miR-223表达的影响因素。结果苯暴露组年龄为(31.17±7.30)岁,C_(TWA)为0.05~0.30 mg/m^(3),为低浓度苯暴露;未暴露组年龄为(32.52±6.15)岁。苯暴露组与未暴露组的年龄、BMI、吸烟和饮酒构成差异均无统计学意义(P>0.05)。苯暴露组miR-155相对表达量中位数为0.953,与未暴露组的1.293比较差异无统计学意义(P>0.05);苯暴露组miR-223相对表达量中位数为0.540,低于未暴露组的1.433,差异有统计学意义(P<0.05)。多因素logistic回归分析结果显示:miR-223表达下调与苯暴露存在统计学关联(OR=2.719,95%CI:1.308~5.651)。结论miR-223表达下调可能与低浓度苯暴露有关。

Objective To investigate the effect of exposure to low concentrations of benzene on miR-155 and miR-223 expression in peripheral blood lymphocytes among workers with benzene exposure.Methods A hundred male employees at a risk of exposure to benzene(the exposed group)were randomly sampled from two small metal products manufacturing enterprises and one medium-sized chemical raw material and chemical products manufacturing enterprise in Ningbo City,Zhejiang Province,and 60 age-matched male employees without benzene exposure were randomly selected as the unexposed group.Age,body mass index(BMI),smoking status,alcohol consumption,disease history,medication history and routine blood testing results of subjects were collected using a questionnaire survey.The 8-hour time weighted average concentration(CTWA)of benzene was measured in the workplace using thermal desorption gas chromatography,and the urine 8-hydroxy-2'deoxyguanosine(8-OHdG)levels were determined using high-performance liquid-chromatography tandem mass spectrometry(HPLC-MS/MS).The miR-155 and miR-223 expression was quantified in peripheral blood lymphocytes using quantitative fluorescent reverse transcription-polymerase chain reaction assay,and the factors affecting miR-155 and miR-223 expression were identified using multivariable logistic regression analysis.Results The subjects in the exposed group had a mean age of(31.17±7.30)years,and were exposed to low concentrations of benzene(C_(TWA),0.05 to 0.30 mg/m^(3)),while the subjects in the unexposed group had a mean age of(32.52±6.15)years.There were no significant differences between the exposed and unexposed groups in terms of age,BMI,proportion of smokers or proportion of alcohol consumers(P>0.05).There was no significant difference in the median relative miR-155 expression between the exposed and unexposed groups(0.953 vs.1.293,P>0.05),and lower median relative miR-223 expression was quantified in the exposed group than in the unexposed group(0.540 vs.1.433,P<0.05).Multivariable logistic regression analysis revealed that down-regulation of miR-223 expression correlated with exposure to benzene(OR=2.719,95%CI:1.308-5.651).Conclusion Down-regulation of miR-223 expression may be associated with exposure to low concentrations of benzene.