中文摘要：

目的探讨吸入性苯染毒导致小鼠周围血细胞遗传损伤与miR-34a表达改变的关系。方法无特定病原体级C57BL/6小鼠64只随机分为对照组和低、中、高剂量组,每组16只,雌雄各半;分别给予质量浓度为0.00、3.24、16.22和81.11 mg/m3的苯连续动式吸入染毒,每天染毒6 h。于连续染毒14和28 d时,各组随机抽取雌雄各半共8只小鼠采集全血后处死,检测周围血血常规、骨髓有核细胞与成熟红细胞比值、骨髓嗜多染红细胞微核率和周围血miR-34a相对表达水平等指标。结果高剂量组小鼠白细胞（WBC）和中性粒细胞（NEUT）的计数均低于其余3组（P〈0.05）;中、高剂量组淋巴细胞（LY）和红细胞（RBC）的计数均低于对照组（P〈0.05）,而微核率和miR-34a相对表达水平均高于对照组（P〈0.05）;3个剂量组小鼠LY和RBC的计数均随染毒剂量的增加而下降,微核率和miR-34a相对表达水平均随染毒剂量的增加而上升（P〈0.05）,均呈剂量-效应关系。小鼠血小板计数和骨髓有核细胞与成熟红细胞比值在染毒剂量和染毒时间主效应及两者的交互效应上均无统计学意义（P〉0.05）。WBC、LY和RBC的计数均与苯染毒剂量呈中度负相关,秩相关系数（rS）分别为-0.598、-0.677和-0.656（P〈0.01）;微核率、miR-34a相对表达水平均与苯染毒剂量呈中度正相关,rS分别为0.790和0.762（P〈0.01）。微核率和miR-34a相对表达水平分别与WBC、LY和RBC的计数呈负相关,rS分别为-0.543、-0.643、-0.522和-0.562、-0.623、-0.554（P〈0.01）;miR-34a相对表达水平与微核率呈中度正相关,rS为0.617（P〈0.01）。结论苯致小鼠周围血细胞计数异常和骨髓细胞遗传损伤时,伴随着miR-34a表达的上调。

英文摘要：

Objective To investigate the correlation between genetic damage of peripheral blood cells in mice caused by benzene inhalation exposure and miR-34a expression changes. Methods Totally 64 specific pathogen free healthy C57BL/6 mice were randomly divided into control group and low-, medium- and high-dose groups, with 16 mice in each group, half male and half fem.,de. The mice were respectively exposed to benzene at the mass concentrations of 0. 00, 3.24, 16. 22 and 81.11 mg/m3 in a continuous dynamic inhalation chamber system, 6 hours per day for 14 or 28 days. On the 14th and the 28th day of exposure, 8 mice with each gender in half were randomly selected from each group, and sacrificed after the whole blood collection. The indexes of peripheral blood routine examination, ratio of nucleated cell to mature red blood cell in bone marrow, micronucleus rate of polychromatie erythroeytes, and relative expression level of miR-34a in peripheral blood were measured. Results The counts of white blood cell （WBC） and neutrophil （NEUT） in the high-dose group were significantly lower than those in other 3 groups （ P 〈 0. 05 ）. In medium- and high-dose groups, the counts of lymphocytes （LY） and red blood cell （RBC） were significantly lower than those in the control group （P 〈 0. 05 ） ; however, their micronucleus rates and relative expression levels of miR-34a were significantly higher than those in the control group （ P 〈 0. 05 ）. Among the 3 experimental groups, with the increase of dose, LY and RBC counts decreased, while the micronucleus rates and relative expression levels of miR-34a increased （ P 〈 0. 05 ） , all showing dose- effect relationship. In all four groups, blood platelet counts and ratio of nucleated cell to mature red blood cell in bone marrow had no statistical significant difference in main effect or interaction effect with contamination dose or exposure time （P 〉 0.05 ）. WBC, LY, and RBC counts were moderately and negatively correlated with dose, and the Spearman