VOCs、细菌及颗粒物混合暴露致小鼠学习记忆障碍机制研究

室内空气污染的现状是多种污染源共存，挥发性有机物(volatile organic compounds, VOCs)、细菌及颗粒物等是典型室内空气污染物。神经行为学毒性是室内空气污染引起的敏感毒性作用之一。为了探讨VOCs、细菌及颗粒物混合暴露对小鼠学习记忆能力的影响及机制，选用雄性昆明小鼠70只，随机分为对照(G1)和2～7(G2～G7)号染毒组。采用水迷宫和抓力仪测定小鼠的学习记忆潜伏期和抓力，染毒结束后测定全脑中活性氧(ROS)、丙二醛(MDA)，神经递质谷氨酸(Glu)、乙酰胆碱(Ach)含量以及胆碱能系统的乙酰胆碱转移酶(ChAT)和乙酰胆碱酯酶(TChE)活力，同时分析脑源性神经营养因子(BDNF)、胶质细胞神经营养因子(GDNF)及神经生长因子(NGF)的水平。结果显示，第6天，G5、G6及G7小鼠的抓力、逃避潜伏期及在原平台所在象限的探索时间较对照组存在显著差异，并且伴有ROS、MDA含量的显著升高，Glu含量的显著升高，Ach含量、ChAT及TChE活力的显著降低，以及神经营养因子的显著下调(P<0.05或P<0.01)。研究结果表明，VOCs、颗粒物及细菌混合暴露能够导致小鼠学习记忆障碍，混合暴露引起的氧化损伤诱导的神经兴奋或抑制性毒性作用，以及神经营养因子沿轴突逆向传递降低或中断两方面作用导致神经递质产生和释放异常，进而引起学习记忆能力降低。

Mechanisms of Dysfunction on Learning and Memory Capacity Induced by VOCs, Bacteria and Particulate Matter

Indoor air pollution is characterized by the coexistence of a variety of sources, while volatile organic compounds, bacteria and particulate matters are representatives of indoor air pollutants. Neurobehavioral toxicity is one of the most sensitive effects that indoor air pollution will induce. In order to investigate the effects and mechanisms of VOCs, bacteria and particulate matter on learning and memory capacity of mice, 70 Kunming male mice were randomly divided into one control group (G1) and six exposure groups (G2-G7). Morris water maze system and the grip strength meter were used to test learning and memory latency and the grip strength of mice. The levels of ROS, MDA, Glu, Ach and activities of cholinergic system enzymes (ChAT, TChE) in brain were analyzed. The expression of BDNF, GDNF and NGF were also evaluated. The results showed that on the sixth day, there were significant differences on grip strength, escape latency, time spent in the target quadrant between the control and G5, G6, G7 group, which were accompanied with the significant increase of the levels of ROS, MDA and Glu, as well as the significant decrease of Ach level, ChAT and TChE activities and neurotrophin expression (P<0.05 or P<0.01). Our findings indicated that VOCs, particulate matter and bacteria can lead to dysfunction on learning and memory capacity of mice. It is speculated that the mechanism might involve the neural excitatory or inhibitory toxicity induced by oxidative damage, and the abnormal production and release of neurotransmitter caused by inhibited- or interrupted- retrograde axonal transport of neurotrophin, which led to the dysfunction of learning and memory capacity subsequently.