十溴联苯醚对小鼠学习记忆能力及海马NOS和NO的影响

Effect of decabromodiphenyl ether on learning/memory ability and hippocampus NOS/NO in mice

目的探讨十溴联苯醚(PBDE-209)暴露对小鼠学习记忆能力的影响和可能机制。方法将18只4周龄雄性ICR小鼠随机分成3组,每组6只。分为溶剂对照组(DMSO组),低剂量染毒组(300 mg/kg),高剂量染毒组(500 mg/kg),每周染毒6次,连续染毒6周。染毒第6周利用Morris水迷宫测定小鼠学习记忆能力(期间继续给药),染毒6周结束后处死老鼠,取一侧海马进行HE染色观察海马组织形态学改变,另一侧海马测定组织NOS活性和NO含量。结果小鼠海马组织的病理切片结果显示:染毒组海马组织CA1区细胞排列紊乱,高剂量染毒组的细胞紊乱更明显。Morris水迷宫实验结果显示,高剂量染毒组和低剂量染毒组小鼠找到平台的平均潜伏期分别为(64.322±4.419)s和(50.912±4.419)s,长于对照组的(23.183±4.419)s(P<0.05)。探索实验结果显示,高剂量染毒组穿越平台次数为(1.83±0.753)次,明显少于对照组的(3.67±0.516)次(P<0.05)。高剂量染毒组和低剂量染毒组小鼠海马NOS活性分别是(1.209±0.241)U/mg prot和(2.198±0.192)U/mg prot,低于对照组的(3.551±0.347)U/mg prot;NO含量分别为(0.099±0.012)μmol/mg prot和(0.325±0.027)μmol/mg prot,低于对照组的(0.544±0.020)μmol/mg prot(P<0.05)。结论 PBDE-209暴露可能抑制海马中NOS活性及NO含量,并影响小鼠学习记忆能力,其间关系值得进一步探讨。

Objective To investigate the effect of deeabromodiphenyl ether （PBDE-209） exposure on learning and memo- ry abilities and its mechanism in mice. Methods All of 18 four-week old male ICR mice were randomly divided into three groups： solvent control group （DMSO group） , high-dose group （500 mg/kg） and low-dose group （300 mg/kg） , n =6, ex- posed to PBDE-209 6 times per week for 6 weeks. The Morris water maze test was used to estimate the learning and memory abil- ities of mice at the 6th week after exposure. After 6 weeks exposure, the mice were sacrificed, taking the hippcampuses for measuring of NOS activity, NO content and histopathological examination. Results h was showed that the arrangement of neu- rons were confused in hippoeampal CA1 area in miee of exposure group, especially the high-dose group. The Morris water maze test showed that the average latency time （seconds） were （64. 322 ±4. 419） and （50. 912±4. 419） respectively in high-dose group and low-dose group, all were longer than that of DMSO group （23. 183 ±4.419） （P 〈0.05）. Exploration test showed that the crossing platform frequence of high-dose group was （ 1.83 ± 0. 753 ） times, significantly less than that of DMSO group （3.67 ±0. 516） times （P 〈0. 05）. The hippocampal NOS activity were （1. 209 ±0. 241） U/mg pro and （2. 198±0. 192） U/mg pro respectively in high-dose group and low-dose group, obviously lower than that of DMSO group （3. 551 ±0. 347） U/ mg pro; the NO levels were （0. 099 ± 0. 012） Ixmol/mg pro and （0. 325 ± 0. 027） μmol/mg pro, respectively, also lower than that of DMSO group （0. 544 ± 0. 020） μ mol/mg pro （P 〈 0. 05）. Conclusion The results suggested that the exposure of PBDE-209 may inhibit hippocampal NOS activity and NO content, and affect learning and memory abilities in mice, the rela- tionship between them is worth of further exploration.