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目的观察邻苯二甲酸二乙基己酯(DEHP)与双酚A(BPA)联合染毒对大鼠神经行为的影响。方法无特定病原体级4周龄健康Wistar大鼠40只随机分为对照组、DEHP组、BPA组和联合染毒组,每组10只,雌雄各半。DEHP组予1 500 mg/kg DEHP染毒,BPA组予200 mg/kg BPA染毒,联合染毒组予750 mg/kg DEHP和100 mg/kg BPA染毒。3个染毒组的受试物用玉米油配制成相应剂量,以5 m L/kg体质量的给药剂量连续灌胃染毒,对照组予等体积玉米油灌胃,每天1次,每周5 d,连续6周。染毒第3和6周时,采用步下法、转棒实验和足迹分析法对大鼠进行神经行为测试。染毒结束后,检测脑脏器系数和脑组织一氧化氮(NO)水平、一氧化氮合酶(NOS)活力。结果染毒第2和6周时,DEHP组和BPA组雌鼠分别有2和1只死亡;染毒期间DEHP组大鼠体质量出现增长缓慢甚至停滞的现象;但3个染毒组大鼠均无出现步态不稳和共济失调现象。染毒第3周时,DEHP组大鼠首次下台时间均低于其余3组(P<0.05);DEHP组大鼠染毒第6周时首次下台时间高于同组染毒第3周(P<0.05);转速为18r/min时,BPA组大鼠在转棒上停留时间分别低于对照组和DEHP组(P<0.05);BPA组大鼠步长分别低于对照组和DEHP组(P<0.05),DEHP组大鼠步宽和步态变异率分别低于其余3组(P<0.05),第3周时联合染毒组大鼠⊿α值低于同时间点对照组(P<0.05),第6周时联合染毒组大鼠⊿α值高于同时间点DEHP组(P<0.05)。染毒结束后,DEHP组大鼠脑脏器系数分别高于其余3组(P<0.05);4组大鼠脑组织NO水平与NOS活力差异均无统计学意义(P>0.05)。结论在本研究的实验条件下,DEHP和BPA分别对大鼠神经行为个别观察指标产生影响,但未见两者的协同毒性作用。
Objective To observe the effects of DEHP and BPA on neurobehavioral activity in rats. Methods Forty Wistar rats aged 4 weeks without specific pathogen were randomly divided into control group, DEHP group, BPA group and combined exposure group, with 10 mice in each group. DEHP group was treated with 1 500 mg / kg DEHP, while BPA group was treated with 200 mg / kg BPA. The combination group was given 750 mg / kg DEHP and 100 mg / kg BPA. The three test groups were treated with corn oil to prepare the corresponding dose of 5 m L / kg body weight of the continuous dose of intragastric administration, the control group was given an equal volume of corn oil gavage once a day, each Week 5 d, for 6 weeks. At the 3rd and 6th week of exposure, the rats were subjected to neurobehavioral testing by the step-down method, the rotarod test and the footprinting method. After the exposure, the indexes of brain organ and nitric oxide (NO), nitric oxide synthase (NOS) activity were detected. Results At the 2nd and 6th week of exposure, there were 2 and 1 deaths in the DEHP and BPA groups, respectively. During the exposure period, the body weight of DEHP group showed slow or even stagnation. However, No gait instability and ataxia occurred. At the third week of exposure, the first step-down time of DEHP group rats was lower than the other three groups (P <0.05); the first step-down time of rats in DEHP group was higher than that of the third group (P (P <0.05). At the speed of 18 r / min, the retention time of rats in BPA group was lower than that of control group and DEHP group (P <0.05), the BPA group rats step length was lower than that of control group and DEHP group (P <0.05). The mutation rate of gait width and gait of rats in DEHP group were lower than those in the other three groups (P <0.05), and the value of ⊿α in rats in combination group was lower than that in the control group <0.05). At the sixth week, the ⊿α values in the joint exposure group were higher than those in the DEHP group (P <0.05). The brain organ coefficient of DEHP group was higher than the other three groups (P <0.05) at the end of exposure. No significant difference was found in NO level and NOS activity between the 4 groups (P> 0.05). Conclusions DEHP and BPA, respectively, affect the neurobehavioral behavior of individual rats under the experimental conditions in this study, but no synergistic toxic effects have been observed.