GABA_A受体激动剂对AD模型配体门控氯通道的作用

目的观察并分析GABA_A受体激动剂蝇蕈醇对GABA激活的配体门控氯通道的作用,为寻找新的抗阿尔茨海默病(AD)药物提供实验依据。方法 Aβ_(1-42)诱导海马神经细胞作为AD细胞模型;通过膜片钳(Patch clamp)技术在大鼠海马神经元上记录配体门控氯通道瞬时外向电流,采用非特异性氯通道阻断剂(NFA)和无GABA的细胞外液确定该电流成份为瞬时外向氯电流;通过膜片钳技术观察GABA_A受体激动剂蝇蕈醇对于在大鼠海马神经元上记录瞬时外向电流的作用;向AD细胞模型中加入GABA_A受体激动剂,采用MTT观察各组细胞活力。结果加入GABA_A受体激动剂蝇蕈醇后GABA激活氯电流强度增加;加入浓度为1 mmol/L蝇蕈醇的AD模型细胞组存活率为(91.32±3.73)%,略高于未加入蝇蕈醇的模型细胞组,两组对比P0.05。结论 GABA_A受体激动剂蝇蕈醇对于AD细胞模型具有保护作用。

The role of GABAA receptor agonist for the ligand-gated chloride channels in the model of Alzheimer's disease

Objective To observe and analyze the role of the GABAA receptor agonist muscimol on the GABA-activated ligand gated chloride channel,in order to provide experimental basis for finding new anti-Alzheimer's disease drugs.Methods Add Aβ1-42 to induce the hippocampal neurons as Alzheimer's disease cell model.Record the transient outward current of ligand-gated chloride channel in rat hippocampal neurons by the technique of patch clamp.Then use non-specific chloride channel blockers (NFA) and non-GABA extracellular fluid to determine the currents recorded in was the transient outward chloride current.Through patch-clamp technique to observe the role of the GABAA receptor agonist muscimol for the transient outward currents in the cell model of Alzheimer's disease.Add GABAA receptor agonist to the cell model of Alzheimer's disease and observe the cell viability of each group by the method of MTT.Results The GABA-activated chloride current intensity was increased by adding the GABAA receptor agonist of muscimol.The survival rate of the rats cell in model of Alzheimer's disease was (91.32±3.73)% by adding a concentration of 1mmol/L muscimol,it was slightly higher than the model cell group without muscimol,the compared result of two groups was P>0.05.Conclusions The GABAA receptor agonist of muscimol has protective effect for the rats cell model of Alzheimer's disease.