氨基脲诱导的大鼠神经行为毒性及其生化机制

The neurobehavioral toxicity and biochemical mechanism of semicarbazide in rats

为探究氨基脲(SEM)染毒对SD大鼠的神经行为毒性及其作用机制,将44只SPF级SD雄性大鼠随机分为4组:对照组,SEM低、中、高剂量组,每组11只,分别以0,7.5,15,30mg/(kg·bw)SEM的剂量连续灌胃染毒28d.染毒前后分别通过旷场实验和高架十字迷宫实验测试神经行为.采用液相色谱法测定γ-氨基丁酸(GABA)和谷氨酸(GLU),ELISA法测定5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)、单胺氧化酶(MAO)以及N-甲基-D-天氡氨酸受体(NMDAR)含量.结果显示,高剂量染毒组大鼠在旷场实验中运动总距离和中央区域距离显著低于对照组(P<0.05),各剂量组大鼠在高架十字迷宫实验中进入开臂时间百分比和进入开臂次数百分比均显著低于对照组(P<0.05或P<0.01).与对照组相比,各染毒组大鼠脑组织中GABA含量和MAO活性均有不同程度降低,而GLU,NMDAR,5-HT,NE和DA水平均有不同程度上升.SEM诱导大鼠神经行为毒性的机制与破坏GABA和GLU的相互转化、增加NMDAR含量以及抑制MAO活性导致单胺类神经递质水平上升3个途径有关.

To study the neurobehavioral toxicity of semicarbazide(SEM)in rats and its biochemical mechanism.A total of44male SD rats were randomly divided into4groups(n=11per group):control group,low-dose group,medium-dose group,and high-dose group.SEM was intragastrically administrates at the dosage of0,7.5,15,30mg/kg(body weight)for28days.The open field test(OFT)and elevated plus maze(EPM)were used to evaluated the neurobehavior in rats before and after exposure to SEM.The gamma-aminobutyric acid(GABA)and glutamate acid(GLU)of hippocampus were determined by liquid chromatography.ELISA method was used to mesure the contents of5-hydroxytryptamine(5-HT),norepinephrine(NE),dopamine(DA),monoamine oxidase(MAO)and N-methyl-d-aspartic acid receptor(NMDAR).The results showed that the total distance traveled and the distance traveled in the center were significantly lower in the high-dose SEM group compared with the control group(P<0.05).The open arm time percentage and open arm entries percentage were significantly lower in the SEM groups than in the control group(P<0.05or P<0.01).Compared with the control group,the concentrations of GABA and the activity of MAO were decreased,whereas the levels of GLU,NMDAR,5-HT,NE and DA were increased in different exposed groups.SEM might affect the nervous system of rats by damaging the mutual transformation of GABA and GLU,increasing the concentration of NMDAR and inhibiting the activity of MAO that directly enhance the levels of monoamine neurotransmitters.