除草剂三氟羧草醚经口暴露对小鼠学习记忆能力的影响

目前,有关三氟羧草醚(Acifluorfen,AF)的神经毒性未见报道且亟待确定.为探讨AF经口暴露对小鼠学习记忆能力的影响及其可能机制,将30只雄性昆明小鼠随机分成生理盐水对照组、0.13、1.3、13和130 mg·kg~(-1)·d~(-1) AF染毒组共5组,灌胃染毒14 d,进行Morris水迷宫实验,观察脑海马病理切片,并检测脑组织中活性氧(ROS)、丙二醛(MDA)、还原型谷胱甘肽(GSH)、磷酸化cAMP反应元件结合蛋白(pCREB)和脑源性神经营养因子(BDNF)含量.结果显示,与对照组相比,AF染毒剂量分别为13和130 mg·kg~(-1)·d~(-1)时,小鼠行为学上学习记忆能力下降;海马细胞排列松散;出现氧化损伤,其中,ROS含量显著升高(p0.05),GSH含量显著减少(p0.05);神经保护能力减弱,其中,pCREB和BDNF水平显著(p0.05)或极显著(p0.01)下降.结果表明,AF能够导致小鼠学习记忆能力下降,氧化应激和CREB-BDNF通路级联下调可能是AF造成神经毒性的机制之一.

Effects of acifluorfen on the learning and memory in mice by gavage

The neurotoxicity of acifluorfen (AF) has not been reported, and is needed to be further studied. To investigate the effect of AF on learning and memory of mice and its mechanism, 30 male Kunming mice were divided into 5 groups. Four experimental groups were gavaged with different dosages of AF (0.13, 1.3, 13 and 130 mg·kg^-1·d^-1), while the control was treated using saline solution. The Morris water maze experiment began on the 6th day to measure the ability of learning and memory of mice. The changes in hippocampus morphology by H&E staining, the levels of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), phosphorylated cAMP response element binding protein (pCREB) and brain-derived neurophic factor (BDNF) were assayed, respectively. Compared with the control group, AF at 13 and 130 mg·kg^-1 decreased the ability of learning and memory of mice and loosed the arrangement of hippocampal cells. Also, oxidative stress occurred:the levels of ROS increased while the levels of GSH decreased (p<0.05). The levels of pCREB and BDNF were down-regulated significantly (p<0.05) or very significantly (p<0.01), suggesting that exposure to AF (13 and 130 mg·kg^-1·d^-1) could damage the neuroprotective effects. Taken together, AF can decrease ability of learning and memory of mice, and the mechanism may be related to oxidative damage and the down-regulation of the CREB-BDNF pathway in brain tissue.