毒鼠强对小鼠脑组织GABA_A受体γ_2亚单位mRNA的影响

Effects of tetramethylenedisulfotetramine on the γ_2 subunit of the γ-aminobutyric acid type a receptor of mice's brain

目的观察毒鼠强(TET)染毒前后及药物治疗前后小鼠脑组织GABA_A受体γ_2亚单位mRNA水平的改变以探讨其作用机制。方法小鼠随机分为生理盐水组、低剂量TET组、高剂量TET组、安定干预组、维生素B_6干预组,用药后记录小鼠首次惊厥发生时间、死亡时间及120 min内死亡数。分离大脑、小脑、脑干、海马,行RT-PCR检测GABA_A受体γ_2亚单位。结果①单用大剂量安定可延迟TET中毒小鼠惊厥潜伏期、死亡时间；单用大剂量维生素B_6则不能延迟。②TET导致GABA_A受体γ_2亚单位mRNA上调,且用量与该受体数目呈线性正相关。结论TET是通过拮抗GABA_A受体而发挥毒效应的。

Objective To observe whether the γ2 subunit of the γ-aminobutyric acid type A receptor of mice changes when the little mice are poisoned by tetramethylenedisulfotetramine （TET） and treated by medicine. Method Mice were divided into five groups randomly： physiological saline （NS） group, low-dose TET （LTET） group, high-dose TET （HTET） group, valium-intervene （Val） group and VitB6-intervene （VitB6） group. The time of first convulsion oecured, the time of death and the total numbers of the death within 120 minutes after administration of TET and medicine were recorded. The dead mice＇s cerebrum, cerebellum, brain stem, hippoeampi were separated. The effects of mRNA of γ2 subunit of the γ- aminobutyric acid type A receptor on different parts of the brain were assayed by RT-PCR. Results （1）A big dosage of valium could delay the latent period of convulsion and the death time, and reduce the morality. Large dose of VitB6 did not show any protective effect. （2）TET could up-regulate mRNA of the y, subunit of the γ-aminobutyrie acid type A receptor of little mice＇ brain. The dosage of TET had positively linear relationship with the number of the receptor. When a large dose of valium alleviated clinical syndrome, the number of GABAA receptor was down-regulated. When a large dose of VitB6 did not alleviate the clinical syndrome, TET intoxication and the number of GABAA receptor accordingly had no obvious change. Conclusion TET exert its action through antagonizing the GABAA receptor.