BackgroundFormaldehyde and benzene homologues are common environmental pollutants, and their neurotoxicity has aroused widespread concern.ObjectiveTo investigate the effect of taurine on cognitive impairment after exposure to formaldehyde and benzene analogues in young rats.MethodsTwenty four-week old SD rats were randomly divided into four groups, with six rats in each group: control group (clean air), model group (5 mg·m−3 formaldehyde + 5 mg·m−3 benzene + 10 mg·m−3 toluene + 10 mg·m−3 xylene), low-dose taurine intervention group (5 g·L−1 taurine + mixture of formaldehyde and benzene analogues), and high-dose taurine intervention group (10 g·L−1 taurine + formaldehyde and mixture of benzene analogues), and the exposure was administered by oral and nasal aerosol inhalation for 28 d. At the end of exposure, the learning and memory ability of rats in each group was measured by Morris water maze test. After the behavioral test, the rats were anesthetized and neutralized, and the brain tissue was harvested for histopathological and molecular biological tests. The apoptosis rate of neurons in hippocampal CA1 area was detected by Tunel assay, and the expression levels of apoptosis-related proteins such as caspase 3, bax, and bcl-2 in hippocampal tissue were detected by Western blotting.ResultsThe growth and development of rats in each group were good during inhalation. During the Morris water maze experiment, the escape latencies of rats in the taurine intervention groups were not different from that in the control group (P>0.05) from day 3 to day 5 of training, while the escape latency of rats in the model group was significantly higher than that in the control group (P <0.05). The number of crossing platform and the target quadrant residence time in the high-dose taurine intervention group were not different from those in the control group (P>0.05), while the two variables in the model group and low-dose taurine intervention group were significantly lower than those in the control group (P <0.05). The apoptotic rates of neurons in the hippocampal CA1 area of rats in the control group, model group, and low-dose and high-dose taurine intervention groups were 5.11%, 18.87%, 9.39%, and 4.63%, respectively. The apoptotic rate in the model group was higher than those in the control group and low-dose and high-dose taurine intervention groups (P<0.05). The expression levels of caspase 3, bax, and bcl-2 in the hippocampus of rats in the low-dose and high-dose taurine intervention groups showed no difference compared with the control group (P>0.05). The expression levels of caspase 3 and bax in the model group were higher than those in the control group and low-dose or high-dose taurine intervention groups (P<0.05), and the expression levels of bcl-2 was lower (P<0.05).ConclusionThe mixed exposure to formaldehyde and benzene analogues can damage the learning and memory ability of young rats, and increase the apoptosis of neurons in hippocampal CA1 region. Taurine can reverse the damage induced by formaldehyde and benzene analogues.

为研究小鼠急性经口暴露1,1-二氨基-2,2-二硝基乙烯(FOX-7)的组织分布及代谢特征,将18只KM小鼠随机分为空白组和140、350 mg/kg FOX-7染毒组,单次经口灌胃染毒,采用生物发光成像技术分析发现,FOX-7于小鼠肾脏蓄积约4 h后经肾脏代谢,并较为清晰地展示出小鼠急性经口暴露FOX-7后的组织分布及代谢数据.

[背景]奥克托今(HMX)是当今综合性能最好的单质炸药.有研究发现HMX可影响职业暴露者神经行为功能和周围神经传导速度.3,7-二硝基-1,3,5,7-四氮杂双环[3,3,1]壬烷(DPT)是合成HMX的主要中间体,但目前国内外关于DPT的毒性研究尚未见报道.[目的]探讨HMX及DPT对中国仓鼠肺细胞(CHL)细胞凋亡及氧化应激水平的影响.[方法]应用含有0、31.25、62.50、125、250、500 mg·L-1质量浓度(后称浓度)的HMX、DPT分别对体外培养的CHL染毒24h,利用CCK-8法检测细胞活力;Annexin V-FITC/PI双染法检测细胞凋亡情况;DCFH-DA荧光探针检测细胞内活性氧(ROS)荧光强度.采用抗氧化剂干预,即2.5mmol·L-1 N-乙酰半胱氨酸(NAC)预处理CHL4h,经120 mg·L-1 DPT染毒24h后检测细胞活力和凋亡情况.[结果]细胞活力检测结果显示DPT对CHL的半数抑制浓度为119.55 mg·L-1.当DPT浓度为250 mg·L-1时,细胞活力下降至(17.95±2.18)％;HMX浓度为500 mg·L-1时,细胞活力为(83.34±3.03)％.细胞凋亡结果显示,与各自对照组相比,各染毒组的凋亡率均随染毒剂量增加而逐渐升高(P＜0.05).62.50～500 mg·L-1范围内,HMX导致的细胞凋亡率由(15.63±0.58)％缓慢升至(37.00±1.25)％,而DPT引起的细胞凋亡率从(33.75±0.57)％迅速升至(96.57±0.53)％.细胞内ROS检测结果显示,HMX和DPT均能引起细胞内ROS水平升高.但HMX引起细胞内ROS变化较小,250、500 mg·L-1HMX组细胞内ROS荧光强度分别为103.96±5.59和119.61±4.42,而相同剂量DPT组的ROS荧光强度分别为238.52±7.15和451.02±13.02 (P＜0.05).另外,NAC干预可有效缓解DPT引起的细胞活力抑制和凋亡,NAC预处理+DPT组的细胞活力、凋亡率为(76.41±4.91)％、(16.85±0.12)％,而DPT组为(48.02±2.63)％、(62.67±8.49)％(P＜0.05).[结论]相同剂量下DPT对CHL的毒性大于HMX,高剂量DPT引起细胞内ROS水平升高,导致细胞凋亡.

建立大鼠血液中1,1-二氨基-2,2-二-硝基乙烯(FOX-7)的检测方法,将30只健康SPF级SD大鼠随机分为空白对照组、200和500 mg/kg FOX-7染毒组,每组10只.采用一次性经口灌胃方式染毒,染毒容量为1 ml/100 g.于染毒后第0.5、1、2、4、8、12、24h对大鼠进行眼眶后静脉丛采血,使用紫外可见分光光度计检测血中FOX-7浓度.使用Phoenix WinNonlin 6.1软件进行血药浓度-时间数据分析与毒代参数计算.大鼠单次灌胃FOX-7 200和500 mg/kg后,药-时曲线下面积AUC(o-24)分别为(27.01±1.94) μg/(h·L)和(29.26±3.31)μg/(h ·L),AUC(0-∞)分别为(42.01±2.18)μg/(h·L)和(41.51±3.66) μg/(h·L);达峰浓度Cmax分别为(1.82±0.12) μg/ml和(2.33±0.20) μg/ml,达峰时间tmax为2h;半衰期t1/2分别为(10.83±2.77)h和(8.66±3.01)h.本研究为FOX-7毒代动力学模型的完善提供了科学依据.

为评价1,1-二氨基-2,2-二硝基乙烯(FOX-7)对雄性大鼠性激素水平的影响,将受试物采用3个剂量(199.1、99.6、49.8 mg/kg)染毒,同时设溶剂对照组(4％淀粉溶液).将40只健康SPF级雄性SD大鼠随机分为4组,每组10只,每日固定时间采用经口灌胃方式染毒,染毒容量为1 ml/100 g,连续14 d.于第0天、第7天、第14天称量大鼠体重,禁食12 h后,于第15天对大鼠进行腹主动脉采血,使用ELISA试剂盒检测雌二醇(E2)、促卵泡素(FSH)、黄体生成素(LH)、睾酮(T)、促性腺激素释放激素(GnRH)含量.结果 显示,与溶剂对照组比较,FOX-7高剂量组大鼠第7天和第14天体重显著下降(P＜0.05),性激素T、FSH、LH、E2和GnRH含量均显著降低(P＜0.05).提示高剂量的FOX-7可能会引起雄性大鼠性激素水平紊乱,生殖系统损伤.

为评价1,1-二氨基-2,2-二硝基乙烯(FOX-7)对大鼠睾丸标志酶活力的影响,将40只健康7～12周龄SPF级雄性SD大鼠随机分为4组,分别为溶剂对照(4％淀粉溶液)组和49.8、99.6、199.1 mg/kg FOX-7染毒组,每组10只.采用经口灌胃方式进行染毒,每天1次,连续14d.检测大鼠睾丸组织中的睾丸标志酶γ-谷氨酰转肽酶(γ-GT)、乳酸脱氢酶(LDH)、酸性磷酸酶(ACP)、碱性磷酸酶(AKP)的活力.结果 显示,与溶剂对照组比较,99.6、199.1 mg/kg FOX-7染毒组大鼠睾丸组织中LDH的活力降低,各剂量FOX-7染毒组大鼠睾丸组织中AKP的活力降低,差异均有统计学意义(P＜0.05);而各剂量组大鼠睾丸组织中ACP、γ-GT的活力均无明显改变.提示FOX-7可能对雄性大鼠具有一定的生殖毒性.