乙体氯氰菊酯对小鼠大脑皮质γ-氨基丁酸水平及相关酶和受体的影响

Effects of beta-cypermethrin on γ-aminobutyric acid level,relevant enzyme and receptor in the cerebral cortex of mice

目的探讨乙体氯氰菊酯的神经毒性,为该类农药的中毒防治提供理论依据。方法 80只健康成年昆明种小鼠按体质量随机分为4组,每组20只,雌雄各半。染毒组小鼠以一次经口灌胃方式分别给予20、40、80 mg/kg剂量的乙体氯氰菊酯,食用油稀释受试物质,对照组给予等量食用油。于灌胃后2、4 h,每组各取10只小鼠大脑皮质,HPLC法检测γ-氨基丁酸(γ-aminobutyric acid,GABA)水平(μmol/g),分光光度法检测γ-氨基丁酸转氨酶(GABA transaminase,GABAT)活力(nmol/min.mg.pro),Real time RT-PCR法检测GABA受体(GABA-A、GABA-B)mRNA水平。结果染毒后2、4 h,80 mg/kg剂量组小鼠大脑皮质GABA水平(99.77±13.80、108.29±29.67)高于对照组(72.10±20.51、72.09±20.49)(P<0.05);染毒后2 h,40、80 mg/kg剂量组小鼠大脑皮质GABA-T活力(12.45±2.20、11.48±1.33)低于对照组(14.09±1.64)(分别为P<0.05、P<0.01);染毒后4 h,80 mg/kg剂量组小鼠大脑皮质GABA-A mRNA表达(0.89±0.07)低于对照组(1.00±0.08)(P<0.05),GABA-B mRNA表达与对照组比较,差异均无统计学意义(P>0.05)。结论乙体氯氰菊酯可降低小鼠大脑皮质GABA-T活力,使GABA增多,进而反馈性抑制GABA-A受体mRNA表达。

Objective To explore the neurotoxicity of beta-cypermethrin and to provide a theoretical basis for its poisoning pre- vention and treatment. Methods Eighty healthy adult Kunming mice were randomly divided into four groups, with 20 mice in each group （ 10 males and 10 females）. Three experimental groups were respectively administered with 20, 40 and 80 mg/kg beta -cypermethrin dissolved in edible oil by a single oral garage. The control group was administered with edible oil. Ten mice in each group were killed at 2 and 4 hours after administration and cerebral cortex was collected. Then the level of gamma-aminobutyric acid （GABA） , GABA transaminase （GABA-T） activity and GABA receptor （GABA-A and GABA-B） mRNA expression in the cerebral cortex were detected by high performance liquid chromatograph （ HPLC ） , spectrophotometry and real-time RT-PCR re- spectively. Results GABA levels（ μmol/g} in the cerebral cortex of mice administrated with 80 mg/kg of beta-cypermethrin at 2 and 4 hours after the treatment were both higher than those of the control group （ （99.77±13.80} vs. （72.10±20.51 } , （ 108.29 ±29.67） vs. （72.09±20.49） , both P〈0.05）. And GABA-T activity （nmol/min.mg.pro） in the cerebral cortex of mice administra- ted with 40 mg/kg and 80 mg/kg of beta-cypermethrin at 2 hours after the treatment （ （12.45±2.20） , （ 11.48± 1.33） ） were both lower than that of the control group （ （14.09±1.64） , P〈0.05 and P〈0.01 ）. Four hours after the administration, the GABA-A mRNA expression in the cerebral cortex of mice administrated with 80 mg/kg of beta-eypermethrin was significantly decreased compared with the control group （（0.89±0.07） vs. （ 1.00±0.08）, P〈0.05）, while the GABA-B mRNA expression was not statis- tically different （P〉0.05）. Conclusions Beta-eypermethrin can decrease GABA-T activity and increase GABA levels in the cerebral cortex of mice. And then the expression of GABA-A receptor mRNA is inhibited by feedback.