大剂量γ-氨基丁酸与二巯基丙磺酸钠联合维生素B_6对急性毒鼠强中毒大鼠大脑损伤的保护作用

The Protective Effects of Combination Use of High Dose γ-aminobutyric Acid,Sodium Dimercaptopropanesulfonate and Vitamin B_6 on Brain in Rats with Acute Tetramine Intoxication

目的观察大剂量γ-氨基丁酸(GABA)与二巯基丙磺酸钠(Na-DMPS)联合维生素B6(VitB6)对毒鼠强(TET)急性中毒大鼠的治疗及对中毒大鼠大脑保护作用,并与单纯使用大剂量γ-氨基丁酸(GABA)、二巯基丙磺酸钠(Na-DMPS)解毒效果相比较,为临床提供实验基础。方法 30只SD大鼠随机分为:正常对照组、单纯染毒组、单纯大剂量GABA治疗组、单纯Na-DMPS治疗组、大剂量GABA与Na-DMPS联合VitB6联合用药治疗组,每组6只。除正常对照生理盐水灌胃外,其余各组大鼠通过TET灌胃制造大鼠急性中毒模型。染毒后即刻给予大剂量GABA与Na-DMPS联合VitB6、大剂量GABA、NA-DMPS或生理盐水。大鼠死亡前立即或2h后取血测血清NSE、S-100β蛋白,并观察各组脑组织的病理学改变。结果单纯大剂量GABA治疗组、单纯Na-DMPS治疗组、大剂量GABA与Na-DMPS联合维生素B6联合用药治疗组均能有效缓解中毒大鼠症状,延长抽搐潜伏期及惊厥潜伏期。染毒即刻使用联合药物治疗在延长中毒大鼠惊厥潜伏期方面的治疗效果要优于单纯使用大剂量GABA或Na-DMPS治疗;单纯染毒组大鼠血清中NSE、S-100β蛋白的含量显著增高。各治疗组血清NSE、S-100β蛋白与单纯染毒组比较显著降低,联合用药组血清NSE、S-100β蛋白均较单纯给药组低与正常对照组差别不明显;各治疗组大鼠脑组织病理改变均较单纯染毒组大鼠病理改变轻,联合用药组大鼠的脑组织病理改变最轻。结论大剂量GABA与NA-DMPS联合VitB6联合用药方案的治疗急性毒鼠强中毒的效果优于单纯使用大剂量GABA、NA-DMPS;大鼠血清中NSE、S-100β蛋白水平的变化,可作为评估毒鼠强中毒脑组织损伤及治疗效果的指标。

ObjectiveTo observe the protective effects of combination use of high dose γ- aminobutyric acid （GABA）, sodium dimercaptopropanesulfonate （Na-DMPS） and vitamin B6 on brain by comparing their effects with those of single treatment with GABA or Na-DMPS on rats with acute tetramine intoxication. MethodsThirty rats were randomizely into control group （n=6）, pure tetramine treated group （n=6）, GABA group （n=6）, Na-DMPS group （n=6） and combination group （GABA＋ Na-DMPS＋ VitB6, GNDV,n=6）. Neuron-specific enolase （NSE）,S-100βprotein and the pathologic changes of brain in rats were determined to observe the antidotal effects after 2 hours of different drugs （GNDV, GABA or NaDMPS） being administrated to rats with acute tetramine intoxication. ResultsPoisoned symptoms were obviously improved and convulsion/muscular twitch were obviously delayed in poisoned rats administrated with GABA, Na-DMPS or GNDV as compared with rats with pure tetramine intoxication. The therapeutic effects of GNDV were significantly better than other groups. The level of serum NSE,S-100β was significantly higher in rats with pure tetramine intoxication than those treated with GABA, Na-DMPS or GNDV. It seemed that GNDV produced more significantly therapeutic effects because serum NSE,S-100βwere significantly lower than those administrated only with GABA or Na-DMPS. Pathologic damages in brain of rats treatment with GNDV were significantly lighter than those treatment with GABA or Na-DMPS. ConclusionThe combination use of high dose γ- aminobutyric acid, sodium dimercaptopropanesulfonate and vitaminB6 can more effectively heal acute tetramine intoxication. The variation of serum NSE and S-100βprotein is to be an index to envaluate injured level of brain tissue and the therapeutic effect of acute tetramine intoxication.