老年性痴呆大鼠M型乙酰胆碱受体功能变化的研究

The alteration of M-type acetylcholine receptors’function in the rat with Alzheimer’s disease

目的 :探讨老年性痴呆大鼠M型乙酰胆碱受体功能变化。方法 :建立老年性痴呆 (Alzheimer’sdisease,AD)大鼠模型 ,抽提AD大鼠脑半球基底团多聚腺嘌呤mRNA ,注射到非洲爪蟾卵母细胞上表达有功能的大鼠脑乙酰胆碱受体 ,利用电压钳技术记录电压依赖性的离子通道电流。比较AD大鼠组与正常对照组乙酰胆碱 (ACh)引起的M型乙酰胆碱受体电流变化。结果 :①AD组和对照组每克脑组织提取的poly(A) +mRNA分别为 (18± 6 .2 ) μg ,(19± 5 .8) μg ,两者无统计学差异 ;②Cl-是表达的M型ACh电流的主要载流离子 ;③注射老年大鼠海马组织mRNA后 ,ACh诱发的电流幅度 (8.12± 2 .2 1)nA下降 ,比对照组 (2 1.32nA)约下降 (37± 2 .77) % ,差异有极显著性 (P <0 .0 0 1)。结论 :AD大鼠M型乙酰胆碱受体功能呈减弱趋势 ,其原因可能是受体蛋白遗传信息发生了改变。

Objective To investigate the altera ti on of rat's M-type acetylcholine receptors' function in the rat with Alzheimer's disease. Methods The model of the rat with Alzheimer's di sease was established. Poly(A)+mRNA was isolated from hippocampus of the rat's b rain and was microinjected into hippocampus to express functional ion channels. Voltage clamp technique was used to record the current of the voltage-dependent ion channels. The alterations of ACh-inducing current were compared between the rat with Alzheimer’s disease and the controlled group.Results①The poly(A) mRNA isolated from hippocampus of the rat’s brain with Alzhe imer’s disease andthe controlled group were (18±6.2) μg, (19±5.8) μg ,respectively (P>0.05).②The reversal potential of current induced by ACh w as about -20mV, indicating that Cl- was the main carrier ion of current induced by ACh.③The current amplitude induced by ACh in oocytes injected with mRNA isol ated from the rat with Alzheimer’s disease brain and the controlled group were (8.12 2.21 nA),(21.32 nA),respectively(P<0.001).Conclusions The functions of M-type acetylcholine receptors in the rat with Alzheimer' s disease were reduced. The deficiency of expression of receptor in the rat with Alzheimer's disease probably accounts for the reduction of current induced by A Ch.