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目的探讨丙烯酰胺(ACR)染毒致大鼠大脑皮层和小脑谷氨酸(Glutamate,Glu)和γ-氨基丁酸(γ-aminobutyric acid,GABA)的含量变化。方法 60只雄性SD大鼠分为6组,即11 d试验组(生理盐水对照组、30 mg/kg ACR染毒组和50 mg/kg ACR染毒组)和21 d试验组(生理盐水对照组、15 mg/kg ACR染毒组和30 mg/kg ACR染毒组);步态评分评价神经行为改变;LC-MS/MS法测定染毒终点大脑皮层和小脑Glu和GABA含量变化。结果 11 d试验组在染毒终点时,50 mg/kg ACR染毒组与生理盐水对照组、30 mg/kg ACR染毒组相比,体重显著降低(P<0.05),步态评分显著增高(P<0.05);21d试验组在染毒终点时,30 mg/kg ACR染毒组与生理盐水对照组、15 mg/kg ACR染毒组相比,体重显著降低(P<0.05),步态评分显著增高(P<0.05);30 mg/kg 21 d和50 mg/kg 11 d染毒组与对照组相比,大脑皮层和小脑内兴奋性神经递质Glu含量显著降低(P<0.05),且降低幅度一致。结论 ACR引起大鼠大脑皮层和小脑内兴奋性神经递质Glu含量的降低,可能是导致其神经毒性的致病机制之一。
Objective To investigate the changes of glutamate (Glu) and γ-aminobutyric acid (GABA) in cerebral cortex and cerebellum induced by acrylamide (ACR) in rats. Methods Sixty male Sprague-Dawley rats were randomly divided into 6 groups, namely 11-day experimental group (saline control group, 30 mg / kg ACR and 50 mg / kg ACR) and 21-day experimental group Group, 15 mg / kg ACR group and 30 mg / kg ACR group). The gait score was used to evaluate the neurobehavioral changes. The levels of Glu and GABA in the cerebral cortex and cerebellum were determined by LC-MS / MS. Results At the end of 11 d, the body weight was significantly decreased (P <0.05) and the gait score was significantly higher in the 50 mg / kg ACR group compared with the saline control group and the 30 mg / kg ACR group (P <0.05). At the end of treatment, the body weight of 21-day experimental group was significantly lower (P <0.05) compared with the control group and the 15 mg / kg ACR-treated group (P <0.05). Compared with the control group, the content of neurotransmitter Glu in the cerebral cortex and cerebellum decreased significantly at 21 and 50 mg / kg for 11 days (P <0.05) ), And reduce the same rate. Conclusion ACR can reduce the level of Glu, an excitatory neurotransmitter in rat cerebral cortex and cerebellum, which may be one of the pathogenic mechanisms that lead to neurotoxicity.