摘要目的 研究二烯丙基一硫(DAS)拮抗苯诱导大鼠外周血白细胞(WBC)降低中抗氧化作用的相关机制.方法 SPF级成年雄性SD大鼠60只,体重180～220 g,适应性喂养5 d后,随机分为空白对照组、DAS对照组、苯模型组以及苯+DAS低、中、高剂量组,每组10只. DAS各剂量干预组和DAS对照组大鼠分别经口灌胃40、80、160、160 mg/kg·bw DAS,空白对照组和苯模型组给予等体积玉米油;2 h后,苯模型组和DAS各剂量干预组给予苯(1.3 g/kg·bw)-玉米油混合液(体积分数50%),空白对照组和DAS对照组给予等体积玉米油. 1次/d,连续4周.提前1 d颈静脉取抗凝血进行外周血细胞计数;腹腔注射戊巴比妥(50 mg/kg·bw)麻醉大鼠,腹主动脉法取血并分离血清,低温剥离胸腺、脾脏和股骨,检测样品中氧化和抗氧化指标;分离一侧股骨进行骨髓中WBC计数.结果 与空白对照组比较,苯模型组大鼠脾脏、胸腺体积减小,重量及脏器系数均降低(P<0.05);与苯模型组比较,DAS各剂量干预组大鼠脾脏和胸腺体积增大,脾脏重量及系数均升高(P<0.05),苯+DAS中、高剂量组胸腺重量及系数均升高(P<0.05).与空白对照组比较,苯模型组大鼠外周血细胞和骨髓中WBC计数均降低(P<0.05);与苯模型组比较,苯+DAS中、高剂量组外周血细胞和骨髓中WBC计数均升高(P<0.05).与空白对照组比较,苯模型组大鼠血清中丙二醛(MDA)浓度增加(P<0.05),总超氧化物歧化酶(T-SOD)活力、还原型谷胱甘肽(GSH)含量、还原型谷胱甘肽与氧化型谷胱甘肽比值(GSH/GSSG值)以及总抗氧化能力(T-AOC)水平均降低(P<0.05);与苯模型组比较,苯+DAS高剂量组MDA浓度降低(P<0.05),T-SOD活力、GSH含量、GSH/GSSG值以及T-AOC水平均增加(P<0.05).与空白对照组比较,苯模型组大鼠脾脏中MDA浓度增加(P<0.05),GSH含量、GSH/GSSG值和T-AOC水平均降低(P<0.05);与苯模型组比较,DAS各剂量干预组MDA浓度均降低(P<0.05),苯+DAS高剂量组T-SOD活力和GSH/GSSG值以及DAS各剂量干预组GSH和T-AOC水平均增加(P<0.05).与空白对照组比较,苯模型组大鼠骨髓细胞(BMCs)和外周血单个核细胞(PBMCs)中MDA浓度均增加(P<0.05),PBMCs中T-AOC水平降低(P<0.05);与苯模型组比较,DAS各剂量干预组BMCs和PBMCs中MDA浓度降低(P<0.05),苯+DAS高剂量组GSH含量和GSH/GSSG值均增加(P<0.05).结论 DAS拮抗苯诱导外周血WBC减少的机制可能与其抗氧化应激有关.

abstractsObjective To investigate the antioxidant mechanism of diallyl sulfide (DAS) in antagoniz-ing the reduction in peripheral blood white blood cells (WBC) induced by benzene in rats.Methods A total of 60 specific pathogen-free adult male Sprague-Dawley rats, with a body weight of 180-220 g, were selected, and after 5 days of adaptive feeding, they were randomly divided into blank control group, DAS control group, benzene model group, benzene+low-dose DAS group, benzene+middle-dose DAS group, and benzene+high-dose DAS group, with 10 rats in each group. The rats in the benzene+low-dose DAS group, the benzene+middle-dose DAS group, the benzene+high-dose DAS group, and the DAS control group were given DAS by gavage at a dose of 40, 80, 160, and 160 mg/kg·bw, respectively, and those in the blank control group and the benzene model group were given an equal volume of corn oil; 2 hours later, the rats in the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group were given a mixture of benzene (1.3 g/kg·bw) and corn oil (with a volume fraction of 50%), and those in the blank control group and the DAS control group were given an equal volume of corn oil.The above treatment was given once a day for 4 consecutive weeks.At 1 day before treatment, anticoagulated blood was collected from the jugular vein for peripheral blood cell counting.After anesthesia with intraperitoneally injected pentobarbital(50 mg/kg·bw), blood samples were collected from the abdominal aorta, serum was isolated, and the thymus, the spleen, and the femur were freed at a low temperature to measure oxidative and antioxidant in-dices.The femur at one side was freed for WBC counting in bone marrow.Results Compared with the blank control group, the benzene model group had significant reductions in the volume, weight, and organ coefficient of the spleen and the thymus (P<0.05); compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had significant increases in the volume of the spleen and the thymus and the weight and organ coefficient of the spleen(P<0.05), and the benzene+middle-dose DAS group and the benzene+high-dose DAS group had significant increases in the weight and organ coefficient of the thymus(P<0.05).Compared with the blank control group, the benzene model group had a significant reduction in WBC count in peripheral blood and bone marrow (P<0.05), and compared with the benzene model group, the benzene+middle-dose DAS group and the benzene+high-dose DAS group had a significant increase in WBC count in peripheral blood and bone marrow (P<0.05).Compared with the blank control group, the benzene model group had a significant increase in the serum level of malondialdehyde (MDA) (P<0.05) and significant reductions in total superoxide dismutase (T-SOD) activity, reduced glu-tathione(GSH) level, GSH/oxidized glutathione(GSSG) ratio, total antioxidant capacity(T-AOC) (P<0.05);compared with the benzene model group, the benzene+high-dose DAS group had a significant reduction in the serum level of MDA and significant increases in T-SOD activity, GSH level, GSH/GSSG ratio, and T-AOC(P<0.05).Compared with the blank control group, the benzene model group had a significant increase in the level of MDA (P<0.05) and significant reductions in GSH level, GSH/GSSG ratio, and T-AOC (P<0.05) in the spleen; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had a significant reduction in MDA level(P<0.05) and sig-nificant increases in GSH level and T-AOC (P<0.05), and the benzene+high-dose DAS group had significant increases in T-SOD activity and GSH/GSSG ratio (P<0.05).Compared with the blank control group, the ben-zene model group had a significant increase in the level of MDA in bone marrow cells (BMCs) and peripheral blood mononucleated cells (PBMCs) (P<0.05) and a significant reduction in T-AOC in PBMCs (P<0.05);compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had a significant reduction in the level of MDA in BMCs and PBMCs (P<0.05), and the benzene+high-dose DAS group had significant increases in GSH level and GSH/GSSG ratio (P<0.05). Conclusion DAS can antagonize the benzene-induced reduction in peripheral blood WBC, possibly by exerting an anti-oxidative stress effect.