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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。
Objective To investigate the relationship between the genetic damage of haemocytes and the expression of miR-34a induced by inhaled benzene in mice. Methods Sixty-four C57BL / 6 mice without specific pathogen were randomly divided into control group and low, medium and high dose groups, 16 in each group with half male and female; Of benzene continuous dynamic inhalation exposure, daily exposure to 6 h. At the 14th and 28th day of continuous exposure, 8 mice in each group were randomly selected to collect whole blood and sacrificed. Blood samples were collected from peripheral blood, ratio of bone marrow nucleated cells to mature erythrocytes, and bone marrow polychromatic erythrocytes Rate and peripheral blood miR-34a relative expression levels and other indicators. Results The counts of white blood cells (WBC) and neutrophils (NEUT) in high dose group were lower than those in the other three groups (P <0.05). The counts of lymphocytes (LY) and red blood cells (RBC) (P <0.05), while the micronucleus rate and miR-34a relative expression level were higher than those in the control group (P <0.05). The counts of LY and RBC in 3 doses group increased with the increase of the dose However, the decrease, the micronucleus rate and the relative expression level of miR-34a increased with the increase of the dose (P <0.05), showing a dose-effect relationship. The platelet count and ratio of bone marrow nucleated cells to mature erythrocytes had no significant difference in dose and duration of exposure and the interaction between them (P> 0.05). The counts of WBC, LY and RBC were all negatively correlated with the benzene dose. The rank correlation coefficients (rS) were -0.598, -0.677 and -0.656 respectively (P <0.01). The micronucleus rate and the relative expression of miR-34a There was a moderate positive correlation between the levels of benzene and the doses of benzene, with rS values of 0.790 and 0.762, respectively (P <0.01). The relative expression levels of micronucleus and miR-34a were negatively correlated with the counts of WBC, LY and RBC, respectively, rS were -0.543, -0.643, -0.522 and -0.562, -0.623 and -0.554, respectively The relative expression level of -34a was positively correlated with micronucleus rate (rS = 0.617, P <0.01). Conclusions Benzene induced murine peripheral blood cell count abnormalities and genetic damage in bone marrow cells, accompanied by the expression of miR-34a.