苯短期重复染毒对小鼠外周血单个核细胞免疫功能的影响
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摘要
目的探究苯短期重复染毒对BALB/c小鼠外周血单个核细胞免疫功能的影响。方法选用6～8周雄性BALB/c小鼠,随机分为对照组、低剂量组(50 mg/kg体质量)、中剂量组(150 mg/kg体质量)和高剂量组(500 mg/kg体质量)。采用灌胃的方式进行染毒,每天灌胃1次,每周5 d,连续4周。末次灌胃24 h后采取小鼠外周血进行血细胞计数,用ELISA法测定血浆中Ig G、IL-2和IL-6等免疫分子含量,提取外周血单个核细胞测定其线粒体ROS及ATP含量,分别用TBA法、羟胺法和DTNB法测定血浆中SOD、GSH-Px活力和MDA含量。结果低、中和高剂量组小鼠外周血白细胞、淋巴细胞、红细胞和血红蛋白计数明显低于对照组,中、高剂量组小鼠外周血血小板计数明显低于对照组;低、中和高剂量组小鼠外周血血浆中Ig G、IL-2和IL-6含量明显低于对照组;低、中和高剂量组小鼠外周血单个核细胞线粒体ROS含量明显高于对照组,高剂量组小鼠外周血单个核细胞ATP含量明显低于对照组;中、高剂量组小鼠外周血血浆中SOD、GSH-PX活力明显低于对照组,MDA含量明显高于对照组。结论苯短期重复染毒可以引起小鼠外周血氧化应激,导致小鼠外周血单个核细胞线粒体功能下降,进而抑制外周血单个核细胞免疫功能。
Objective To explore the effects on immune function of peripheral blood mononuclear cell in mice induced by short-term repeated exposure to benzene. Methods Male BALB/c mice aged 6-8 weeks were randomly divided into four groups:control group,low-dose group( 50 mg/kg bodyweight),medium-dose group( 150 mg/kg bodyweight) and high-dose group( 500 mg/kg bodyweight). Mice were exposed to benzene solution through gavage administration every Monday to Friday for 4 consecutive weeks,then peripheral blood cells of mice were collected and counted 24 h after the last administration. The content of Ig G,IL-2 and IL-6 in plasma were detected flow cytometry and the content of ATP was detected with corresponding kits. The content of MDA and activity of SOD and GSH-Px were detected with TBA,Hydroxylamine and DTNB method. Results The leukocytes,lymphocytes,red blood cells and hemoglobin counts of the mice in the low,medium and high-dose groups were significantly lower than those in the control group. The platelet counts of mice in the middle and high-dose groups were significantly lower than those in the control group. The content of Ig G,IL-2 and IL-6 in plasma of mice in the low,medium and high-dose groups were significantly lower than those in the control group. The mitochondrial ROS content in peripheral blood mononuclear cell of mice in the low,medium and high-dose groups was significantly higher than that in the control group and the ATP content of peripheral blood mononuclear cell was significantly lower than that in the control group. The activity of SOD and GSH-PX in plasma of mice in the middle and high-dose groups were significantly lower than those in the control group and the content of MDA was significantly higher than that in the control group. Conclusion Short-term repeated exposure to benzene could cause oxidative stress in peripheral blood of mice,leading to decreased mitochondrial function of peripheral blood mononuclear cell in mice,thereby inhibiting immune function of peripheral blood mononuclear cell.
Objective To explore the effects on immune function of peripheral blood mononuclear cell in mice induced by short-term repeated exposure to benzene. Methods Male BALB/c mice aged 6-8 weeks were randomly divided into four groups:control group,low-dose group( 50 mg/kg bodyweight),medium-dose group( 150 mg/kg bodyweight) and high-dose group( 500 mg/kg bodyweight). Mice were exposed to benzene solution through gavage administration every Monday to Friday for 4 consecutive weeks,then peripheral blood cells of mice were collected and counted 24 h after the last administration. The content of Ig G,IL-2 and IL-6 in plasma were detected flow cytometry and the content of ATP was detected with corresponding kits. The content of MDA and activity of SOD and GSH-Px were detected with TBA,Hydroxylamine and DTNB method. Results The leukocytes,lymphocytes,red blood cells and hemoglobin counts of the mice in the low,medium and high-dose groups were significantly lower than those in the control group. The platelet counts of mice in the middle and high-dose groups were significantly lower than those in the control group. The content of Ig G,IL-2 and IL-6 in plasma of mice in the low,medium and high-dose groups were significantly lower than those in the control group. The mitochondrial ROS content in peripheral blood mononuclear cell of mice in the low,medium and high-dose groups was significantly higher than that in the control group and the ATP content of peripheral blood mononuclear cell was significantly lower than that in the control group. The activity of SOD and GSH-PX in plasma of mice in the middle and high-dose groups were significantly lower than those in the control group and the content of MDA was significantly higher than that in the control group. Conclusion Short-term repeated exposure to benzene could cause oxidative stress in peripheral blood of mice,leading to decreased mitochondrial function of peripheral blood mononuclear cell in mice,thereby inhibiting immune function of peripheral blood mononuclear cell.
引文
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[2]SNYDER R,WITZ G,GOLDSTEIN B D.The toxicology of benzene[J].Environmental Health Perspectives,1993,100(4):293.
[3]DUNN G P,BRUCE A T,IKEDA H,et al.Cancer immunoediting:from immunosurveillance to tumor escape[J].Nature immunology,2002,3(11):991.
[4]PALMER S,ALBERGANTE L,BLACKBURN C C,et al.Thymic involution and rising disease incidence with age[J].Proceedings of the National Academy of Sciences of the United States of America,2018,115(8):1883.
[5]胡秀学,陈晋,杨益萍,等.苯对人外周血单个核细胞S+G2/M期阻滞、细胞凋亡和DNA氧化损伤的影响[J].细胞与分子免疫学杂志,2012,28(9):940.
[6]FABIANI R,DE BARTOLOMEO A,ROSIGNOLI P,et al.Influence of culture conditions on the DNA-damaging effect of benzene and its metabolites in human peripheral blood mononuclear cells[J].Environmental and molecular mutagenesis,2001,37(1):1.
[7]VILLEMAIN F,CHATENOUD L,GUILLIBERT E,et al.Decreased production of interleukin-2 in schizophrenia[J].Annals of the New York Academy of Sciences,1987,496:669.
[8]FINKEL T.Signal transduction by reactive oxygen species[J].Journal of Cell Biology,2011,194(1):7.
[9]BROWN D I,GRIENDLING K K.Regulation of signal transduction by reactive oxygen species in the cardiovascular system[J].Circulation Research,2015,116(3):531.
[10]MALECKI E A.Manganese toxicity is associated with mitochondrial dysfunction and DNA fragmentation in rat primary striatal neurons[J].Brain research bulletin,2001,55(2):225.
[11]PADMANABHAN R,AL-MENHALI N M,TARIQ S,et al.Mitochondrial dysmorphology in the neuroepithelium of rat embryos following a single dose of maternal hyperthermia during gestation[J].Experimental brain research,2006,173(2):298.
[12]GUO Y,SUN J,YE J,et al.Saussurea tridactyla Sch.Bip.-derived polysaccharides and flavones reduce oxidative damage in ultraviolet B-irradiated Ha Ca T cells via a p38MAPK-independent mechanism[J].Drug design,development and therapy,2016,10:389.
[13]HARJU T,KAARTEENAHO-WIIK R,SIRVI R,et al.Manganese superoxide dismutase is increased in the airways of smokers'lungs[J].The European respiratory journal,2004,24(5):765.
[14]LIU C,LI M,CAO Y,et al.Effects of avermectin on immune function and oxidative stress in the pigeon spleen[J].Chemico-biological interactions,2014,210:43.