铝对大鼠海马CA_3区诱发电位的抑制作用与胆碱能、GABA系统的关系

Inhibitive Effect of Aluminium on the Evoked Potential in Hippocampal CA_3 Area and Its Relationship with Cholinergic and GABA System in Rats

目的 研究铝对大鼠海马CA3区诱发电位的抑制作用与胆碱能、GABA系统的关系。方法 实验用SD大鼠68只,单个脉冲刺激穿通纤维(PP),记录海马CA3区诱发的群体峰电位(PS)。待PS稳定后,向海马CA3区微量注射药物,观察铝对海马CA3区诱发电位的影响及某些中枢递质对铝抑制PS效应的影响。结果①海马CA3区局部微量给予0.5 mol/LAlCl3,记录的PS幅值1 min时下降幅度达峰值,为给药前的(33.8±11.0)％(n=6)。AlCl3的这种抑制作用持续120 min。②预先CA3区微量注入1×10^(-9) mol/L Tacrine(胆碱酯酶抑制剂),1 min后再注入AlCl3,结果1-30 min内拮抗了AlCl3抑制PS幅值的效应(n=8),给予1×10^(-8) mol/L Tacrine(n=6),则拮抗作用延长至60 min,而给予1×10^(-10) mol/L Tacrine(n=-6),拮抗作用在3-5 min弱于1×10^(-9) mol/L组。③海马CA3区先给予1×10^(-3)mol/L Bicuculline,1 min后再注入AlCl3,在1-20 min内Bicuculline部分减弱了AlCl3的作用(n=9)。结论一定浓度的铝可抑制海马CA3区的诱发PS幅值;Tacrine能拮抗这种作用,且可能与剂量有关,提示铝的抑制作用可能与损害了ACh递质系统有关;应用GABAA受体阻断剂Bicuculline也使铝对PS抑制效应减弱,表明铝对PS的抑制也可能部分通过GABA途径起作用。

Objective To investigate the effect of aluminium on the evoked potential in hippocampal CA3 area and its relationship with cholinergic and GABA system. Methods Experiments were performed on 68 Sprague-Dawley rats. Single pulse was used to stimulate perforant path (PP) and the population spike (PS) evoked potential was recorded by using extracellular recording method in hippocampal CA3 are-a. After the recorded PS sustained, aluminium and other drugs were microinjected into CA3 area to investigate the effect of aluminium on the evoked potential in hippocampal CA3 area and its relationship with some neurotransmitters. Results Microinjection of 0. 5 mol/L A1Cl3 into the CA3 area in rats could reduce the amplitude of PS (33. 8±11. 0) % of controls (n=6) at one min and the inhibiting effect lasted 120 min. Pre-microinjection of 1×10^(-9) mol/L Tacrine (inhibitor of AChE) into the CA3 area could inhibit the effect of A1Cl3 (0. 5 mol/L) microinjection one min later on PS during 1 to 30 min. 1×10^(-8) mol/L Tacrine pre-microinjection could prolong the inhibiting time to 60 min. Although the inhibiting time was the same as that of 1×10^(-9) mol/L Tacrine, the inhibiting action of 1×10^(10) mol/L Tacrine was weaker than that of the 1×10^(-9) mol/L Tacrine group (n= 6). After 1×10^(-3) mol/L Bicuculline was preinjected into CA3 area followed by A1Cl3 injection one later, it was found that Bicuculline could alleviate the action of A1Cl3 (n = 9) within 1 to 20 min. Conclusion The aluminum can inhibit the amplitude of PS induced in hippocampal CA3 area in rats and Tacrine can reverses this effect probably related with doses, suggesting that the inhibitory effects of aluminum might be related with the damage to ACh system. Bicuculline can also weaken the inhibitory effect of aluminum on PS, indicating the inhibitory effects of aluminum may act through a GABA pathway.