微泵恒速灌注叠氮钠致痴呆大鼠脑内胆碱及单胺类神经递质含量改变

Effect of sodium azide infusion by minipump on cholinergic and dopaminergic neuro-transmitter in the brain of rats

目的观察线粒体呼吸链复合体IV(线粒体细胞色素C氧化酶 )抑制剂叠氮钠对大鼠脑内胆碱及单胺类神经递质的影响 ,探讨线粒体缺陷导致学习记忆障碍的可能机制。方法SD大鼠皮下埋植Alzet微泵 ,连续恒速给予叠氮钠共 3 0天 ,分为 1mg/kg/h和 2mg/kg/h两个剂量组。取脑 ,分区测定皮层和海马胆碱乙酰基转移酶 (放射化学法 )及乙酰胆碱酯酶 (羟胺比色法 )的活性 ;高效液相色谱法测定纹状体内单胺类神经递质及其代谢产物含量。结果模型大鼠皮层和海马胆碱乙酰基转移酶活性降低 ,海马区乙酰胆碱酯酶活性升高 ,皮层和海马胆碱乙酰基转移酶与乙酰胆碱酯酶活性的比值明显降低。纹状体内单胺类神经递质及其代谢产物含量各组间无明显差异。结论线粒体细胞色素C氧化酶活性的抑制可以导致动物脑内胆碱乙酰基转移酶及乙酰胆碱酯酶活性的异常 ,是模型大鼠学习记忆能力障碍的基础。微泵恒速灌注叠氮钠仅损伤大鼠脑内胆碱能神经系统 ,对脑内单胺类神经递质无影响 ,可作为拟痴呆模型 ,应用于发病机理及药理学等方面的研究。

ObjectiveTo observe the influence of mitochondrial cytochrome c oxidase(COX) decrease on cholinergic and dopaminergic system in brain of model rats.MethodsRats were administrated with 1mg/kg/h or 2mg/kg/h subcutaneously via an Alzet minipump for 30 days. Choline-acetyl-transfertase(ChAT) and acetylcholinesterase(AChE) activity in hippocampus and cortex of rats were measured by radiochemical method and hydroxylamine colorimetry separately. The contents of Norepinephrine(NE), dopamine, 5-hydroxytryptamine(5-HT) and their metabolic products in striatum were measured by HPLC.ResultsChAT activity was significantly inhibited in hippocampus and cortex of model rats, however, the activity of AChE increased in hippocampus and was not affected at the cortex. Therefore, the ratio of ChAT/AChE decreased in model rats. The content of NE, dopamine, 5-HT and their metabolic products in striatum were not different among all groups.ConclusionsCOX deficiency can induce abnormality of ChAT and AChE activity in model rats. Dysfunction of neurotransmitter-acetylcholine would be account for learning-memory deficiency. Model rats indicated cholinergic system deficit without any dopaminergic system abnormality, so chronic infusion of sodium azide via minipump may specially serve as a tool for developing the experimental model of Alzheimer's disease. [