新生大鼠啶虫脒亚慢性暴露致成年后神经系统毒性的研究

Sub-chronic Exposure to Acetamiprid in Neonatal Rats Leads to Neurotoxicity in Adulthood

观察新生大鼠啶虫脒(acetamiprid,ACE)慢暴露对成年后神经行为、大脑皮质与海马的影响。选择出生一周的雄性Sprague-Dawley(SD)大鼠18只,随机分为对照组(Control)、ACE-15组(15 mg·kg^(-1)·d^(-1))、ACE-40组(40 mg·kg^(-1)·d^(-1)),每组6只。ACE暴露组灌胃干预9周,期间每周检测体质量。采用开放旷场实验(OFT)、Morris水迷宫(MWM)检测大鼠行为学变化;采用试剂盒检测大脑皮质和海马组织中丙二醛(MDA)和超氧化物歧化酶(SOD)水平;采用Western Blot法检测白细胞介素IL^(-1)β、IL^(-1)0蛋白表达量;采用苏木精-伊红(H&E)染色法检测大脑皮质和海马组织病理学改变;采用Nissl染色法检测大脑海马DG、CA3区神经元变化。OFT结果显示,与对照组相比,ACE暴露组大鼠在中央区运动距离和时间均减少。MWM结果显示,定位巡航期间,暴露组逃逸潜伏期时间增加,目标象限停留时间减少。空间探索期间,ACE-40组跨平台次数减少,目标象限内游泳速度降低。暴露组大鼠脑皮质和海马组织中MDA浓度增高;暴露组大鼠脑皮质SOD活性降低,海马组织SOD活性增高。Western Blot结果显示,与对照组相比,暴露组大鼠皮质和海马组织中IL^(-1)β表达量增高;IL^(-1)0表达量降低。H&E结果显示,ACE-40组海马DG、CA3区神经元出现排列紊乱、层数减少和轮廓模糊。Nissl染色结果显示,暴露组大鼠海马DG、CA3区神经元数量减少,尼氏小体减少。以上结果表明,新生大鼠ACE亚慢性暴露能够导致成年后神经行为变化,可能与脑皮质和海马组织的氧化应激与炎症有关。

To observe the effects of sub-chronic exposure to acetamiprid(ACE)in neonatal rats on neurobehavior,cerebral cortex,and hippocampus in adulthood.18 one-week-old male Sprague-Dawley(SD)rats were randomly divided into control group,ACE-15 group(15 mg·kg^(-1)·d^(-1))and ACE-40 group(40 mg·kg^(-1)·d^(-1)),with 6 rats in each group(n=6).The ACE-exposed groups were given gavage intervention for 9 weeks,during which body weight was measured weekly.Open field test(OFT)and Morris water maze(MWM)were used for neurobehavioral assessment in SD rats;malondialdehyde(MDA)and superoxide dismutase(SOD)levels in cerebral cortex and hippocampus were detected by ELISA kits;IL^(-1)βand IL^(-1)0 expression were detected by Western Blot;hematoxylin and eosin(H&E)staining was used to detect histopathological changes in cerebral cortex and hippocampus;Nissl staining was used to detect neuronal changes in the DG and CA3 regions of the hippocampus.The OFT results showed that the movement distance and duration of movement in the central zone were reduced in the ACE-exposed groups rats compared to the control group.The MWM results showed that the escape latency was increased and the target quadrant residence was decreased in the ACE-exposed group compared with the control group;the target crossing was decreased and the swimming speed in the target quadrant was decreased in the ACE-40 group.The MDA level was increased in the cerebral cortex and hippocampus,whereas the SOD content was decreased in the cerebral cortex but increased in the hippocampus in ACE-exposed groups.Higher expression of IL^(-1)βand lower expression of IL^(-1)0 in the cerebral cortex and hippocampus were also detected in ACE-exposed groups in contrast to the control rats.Disorders of neuronal arrangement,reduced cell layers,and reduced Nissl bodies in the DG and CA3 regions of the hippocampus were observed in ACE-exposed rats.The above results suggest that sub-chronic exposure to ACE in neonatal rats can lead to neurobehavioral changes in adulthood,which may be related to oxidative stress and inflammation in the cerebral cortex and hippocampus.