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目的探讨有机磷农药乐果亚慢性染毒对大鼠学习记忆功能的影响及对中枢兴奋性氨基酸神经递质系统的可能作用。方法48只成年雄性SD大鼠随机分成4组,每组12只。对3个实验组以乐果经口灌胃(5、10和20 mg/kg),每周5 d,每天1次,共13周;对照组给予等体积的生理盐水。染毒结束,每组随机取6只大鼠在Morris水迷宫中检测动物学习记忆功能的改变情况;其余大鼠断头处死进行生化测定。使用硫代乙酰胆碱-二硫代双硝基甲酸(Asch-DTNB)法测定海马中乙酰胆碱酯酶(AChE)活力;用反相高效液相色谱荧光法测定海马中谷氨酸含量;用配体受体结合实验测定N-甲基- D-天门冬氨酸(NMDA)受体的Bmax和Kd值。结果大鼠定位航行实验中,随着训练期的增加,各组动物逃避潜伏期明显缩短;中、高剂量乐果染毒组的潜伏期比对照组长,差异有统计学意义(P<0.05)。空间探索实验中,高剂量组与对照组相比,穿越平台位置的次数明显减少,差异有统计学意义(P<0.05)。动物染毒后,低、中、高染毒组大鼠海马AChE活力分别为对照组的77.9%、62.8%和42.1%,差异有统计学意义,存在剂量一效应关系(P<0.01)。中、高剂量组大鼠海马分区谷氨酸含量与对照组相比增加134.5%、132.9%,差异有统计学意义(P<0.05);中、高剂量组NMDA受体Bmax值与对照组相比降低21.2%、23.2%,差异有统计学意义(P<0.05);各剂量组受体Kd值增加22.2%～33.1%,且高剂量组与对照组比较,差异均有统计学意义(P<0.05)。大鼠的空间记忆能力下降与海马中NMDA受体的亲和力下降在统计学上有相关关系(P<0.05)。结论乐果亚慢性染毒可引起大鼠中枢兴奋性氨基酸神经递质含量及NMDA受体密度和亲和力的改变,并在降低大鼠的学习记忆功能中可能发挥一定的作用。
Objective To investigate the effect of organophosphorus pesticide (ACP) dimethoate on learning and memory in rats and its possible role in the central excitatory amino acid neurotransmitter system. Methods Forty-eight adult male Sprague Dawley rats were randomly divided into 4 groups with 12 rats in each group. Three experimental groups were orally administered orally with dimethoate (5, 10 and 20 mg / kg) for 5 days a week for 13 weeks. The control group was given an equal volume of normal saline. At the end of the treatment, six rats in each group were randomly divided into two groups. Morris water maze test was used to detect the changes of learning and memory in rats. The remaining rats were sacrificed for biochemical determination. The acetylcholinesterase (AChE) activity in the hippocampus was measured by the method of Asch-DTNB. The content of glutamate in the hippocampus was determined by reversed-phase high performance liquid chromatography (HPLC) Bmax and Kd values of N-methyl-D-aspartate (NMDA) receptors were determined in combination with experiments. Results During the navigation experiment, the escape latency of each group was significantly shortened with the increase of training period. The latency of middle and high doses of dimethoate was longer than that of the control group (P <0.05). Compared with the control group, the number of crossing the platform significantly decreased in the high-dose group (P <0.05). The AChE activity in hippocampus of rats in low, middle and high exposure groups was 77.9%, 62.8% and 42.1% respectively after the animals were exposed. The difference was statistically significant, and there was a dose-response relationship (P <0.01). Compared with the control group, the contents of glutamate in hippocampus of rats in medium and high dose groups increased by 134.5% and 132.9%, respectively, with significant difference (P <0.05) (P <0.05). The Kd of each dose group increased by 22.2% -33.1%, and there was significant difference between high dose group and control group (P <0.05). The difference was statistically significant <0.05). There was a statistically significant correlation between decreased spatial memory in rats and decreased affinity of NMDA receptors in the hippocampus (P <0.05). Conclusion Chronic toxicity of dimethoate can cause changes of central excitatory amino acid neurotransmitter and NMDA receptor density and affinity in rats, and may play a role in reducing learning and memory in rats.