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目的:观察脑内同步灌流特异性呼吸链复合体Ⅳ抑制剂叠氮钠(sodium azide,NaN3)对大鼠腹内侧前额叶皮质(mPFC)和海马细胞外液中乙酰胆碱(ACh)和胆碱(Ch)含量的影响,建立线粒体损伤的AD急性模型。方法:应用脑双位点双通道同步微透析采样技术,对清醒自由活动正常大鼠mPFC和海马同步灌流含NaN3(50μmol·L-1)和新斯的明(2μmol·L-1)的改良Ringer氏液120 min,并同步连续收集两脑区的透析液。采用高效液相色谱-柱后固定化酶反应器-电化学法动态监测ACh和Ch含量。结果:正常大鼠的mPFC细胞外液中ACh和Ch含量高于海马区,NaN3在灌流期间能明显降低mPFC/海马细胞外液中ACh,但显著升高Ch,并持续抑制mPFC/海马区ACh和Ch含量恢复。结论:大鼠脑内mPFC和海马同步灌流NaN3使胆碱能神经投射区域功能受损,可造成ACh和Ch代谢紊乱的AD急性模型,可用于病理机制和药理学研究。
OBJECTIVE: To observe the effects of sodium azide (NaN3), a specific respiratory chain-specific complex of respiratory syncytial complex, on the levels of acetylcholine (ACh) and choline (ACh) in rat abdominal ventromedial prefrontal cortex (mPFC) and hippocampus Ch) content of mitochondrial damage to establish an acute model of AD. Methods: The dual-site simultaneous microdialysis sampling technique was used to evaluate the effects of mPFC and synchronous hippocampal infusion of NaN3 (50μmol·L-1) and neostigmine (2μmol·L-1) in conscious and freely moving rats Ringer's solution for 120 min, and simultaneously collect the dialysate of both brain regions simultaneously. The contents of ACh and Ch were monitored by high performance liquid chromatography (HPLC) - post column immobilized enzyme reactor - electrochemical method. Results: The levels of ACh and Ch in mPFC extracellular fluid of normal rats were higher than those in hippocampus. NaN3 significantly decreased ACh in extracellular fluid of mPFC / hippocampus during perfusion but increased Ch, and inhibited ACh and mCFC in hippocampus continuously And Ch content recovery. CONCLUSION: Synapse of NaN3 by mPFC and hippocampus synchronously impaired the function of cholinergic nerve projection area, which can cause ACh and Ch metabolic disorders. It can be used in pathological mechanism and pharmacology research.