铝对大鼠海马CA3区诱发电位的抑制及其与胆碱能、γ-氨基丁酸系统的关系
려대대서해마CA3구유발전위적억제급기여담감능、γ-안기정산계통적관계
Inhibitive effect of aluminium on evoked potentials in hippocampal CA3 region in rats and the relationship with cholinergic and gamma-aminobutyric acid system
  • 万方数据
    中国临床康复 중국림상강복
    CHINESE JOURNAL OF CLINICAL REHABILITATION
    2005年 9期 218-221 ,共4页

    胡剑峰%肖鸿美%李艾

    호검봉%초홍미%리애

    铝%诱发电位%乙酰胆碱%GABA%海马 鋁%誘髮電位%乙酰膽堿%GABA%海馬
    려%유발전위%을선담감%GABA%해마
    背景:以往的研究表明,铝可通过影响细胞内钙稳态、降低蛋白激酶C(PKC)的活性、影响谷氨酸的释放等多种途径影响动物的学习和记忆.含铝饲料喂养的大鼠,其海马CA3区长时程增强(LTP)形成减弱.经进一步采用急性给铝的方法,将三氯化铝(AlCl3)直接微量注射到海马CA3区,观察到铝能减弱海马CA3区的诱发电位、阻抑LTP的产生,这种作用可能与铝损害了L-Arg-NO途径有关.目的:探讨铝对学习记忆的损害及与胆碱能系统和γ-氨基丁酸(GABA)系统的相关性.设计:以实验动物为研究对象,完全随机对照的研究.单位:一所大学生理系、一所职业技术学院医学院.材料:实验于2000-09/2001-04在华中科技大学同济医学院生理系神经电生理实验室完成.实验用SD大鼠68只,由华中科技大学同济医学院实验动物学部提供,普通级,体质量150～250 g,雌雄不拘.干预:SD大鼠随机分为9组,分别为生理盐水组对照组6只,在其海马CA3区内先后(间隔1 min)2次微量注射生理盐水各1 μL;生理盐水+AlCl3组6只,在海马CA3区内先(间隔1 min)微量注射生理盐水与0.5 mol/L AlCl3各1 μL.生理盐水+Tac组6只,在CA3区先后微量注射生理盐水与1×10-9mol/L各Tacrine 1 μL.生理盐水+Bic组6只,在CA3区先后微量注射生理盐水和1×10-3mol/L Bicuculline各1 μL.Tac+AlCl3组:预先分别向大鼠海马CA3区注入1×10-9mol/L(n=8),1×10-10mol/L(n=6)和1×10-8mol/L(n=6)Tacrine 1 μL, min后再注入0.5 mol/L AlCl3 1 μL.Bic+AlCl3组:向海马CA3区先分别注入1×10-3mol/L(n=9),×10-4mol/L(n=7)Bicuculline 1μL, min后再注入0.5 mol/L AlCl3 1μL.单个脉冲刺激穿通纤维(PP)后,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.主要观察指标:海马CA3区诱发的群体峰电位.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/L AlCl3,记录的PS幅度1 min时下降达峰值,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1×10-9mol/L Tacrine(胆碱酯酶抑制剂), min后再注入AlCl3,结果1～30 min内拮抗了AlCl3抑制PS的效应(n=8);给予1×10-8mol/LTacrine(n=6),则拮抗作用延长至60min;而给予1×10-10mol/LTacrine(n=6),拮抗作用在3～5 min弱于1×10-9mol/L组.③海马CA3区先给予1×10-3mol/LBicuculline, 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幅度;Tacrine能拮抗这种作用,且可能与剂量有关.因此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,表明铝的抑制作用也可能部分通过GABA途径起作用.
    배경:이왕적연구표명,려가통과영향세포내개은태、강저단백격매C(PKC)적활성、영향곡안산적석방등다충도경영향동물적학습화기억.함려사료위양적대서,기해마CA3구장시정증강(LTP)형성감약.경진일보채용급성급려적방법,장삼록화려(AlCl3)직접미량주사도해마CA3구,관찰도려능감약해마CA3구적유발전위、조억LTP적산생,저충작용가능여려손해료L-Arg-NO도경유관.목적:탐토려대학습기억적손해급여담감능계통화γ-안기정산(GABA)계통적상관성.설계:이실험동물위연구대상,완전수궤대조적연구.단위:일소대학생리계、일소직업기술학원의학원.재료:실험우2000-09/2001-04재화중과기대학동제의학원생리계신경전생리실험실완성.실험용SD대서68지,유화중과기대학동제의학원실험동물학부제공,보통급,체질량150～250 g,자웅불구.간예:SD대서수궤분위9조,분별위생리염수조대조조6지,재기해마CA3구내선후(간격1 min)2차미량주사생리염수각1 μL;생리염수+AlCl3조6지,재해마CA3구내선(간격1 min)미량주사생리염수여0.5 mol/L AlCl3각1 μL.생리염수+Tac조6지,재CA3구선후미량주사생리염수여1×10-9mol/L각Tacrine 1 μL.생리염수+Bic조6지,재CA3구선후미량주사생리염수화1×10-3mol/L Bicuculline각1 μL.Tac+AlCl3조:예선분별향대서해마CA3구주입1×10-9mol/L(n=8),1×10-10mol/L(n=6)화1×10-8mol/L(n=6)Tacrine 1 μL, min후재주입0.5 mol/L AlCl3 1 μL.Bic+AlCl3조:향해마CA3구선분별주입1×10-3mol/L(n=9),×10-4mol/L(n=7)Bicuculline 1μL, min후재주입0.5 mol/L AlCl3 1μL.단개맥충자격천통섬유(PP)후,기록해마CA3구유발적군체봉전위(PS).대PS은정후,향해마CA3구미량주사약물,관찰려대해마CA3구유발전위적영향급모사중추체질대려억제PS효응적영향.주요관찰지표:해마CA3구유발적군체봉전위.CA3구유발전위적영향급모사중추체질대려억제PS효응적영향.결과:①해마CA3구국부미량급여0.5 mol/L AlCl3,기록적PS폭도1 min시하강체봉치,위급약전적(33.8±11.0)%(n=6).AlCl3적저충억제작용지속120 min.②예선CA3구미량주입1×10-9mol/L Tacrine(담감지매억제제), min후재주입AlCl3,결과1～30 min내길항료AlCl3억제PS적효응(n=8);급여1×10-8mol/LTacrine(n=6),칙길항작용연장지60min;이급여1×10-10mol/LTacrine(n=6),길항작용재3～5 min약우1×10-9mol/L조.③해마CA3구선급여1×10-3mol/LBicuculline, min후재주입AlCl3,재1～20 min내Bicuculline부분감약료AlCl3적작용(n=9).결론:일정농도적려가억제해마CA3구적유발PS폭도;Tacrine능길항저충작용,차가능여제량유관.인차제시려적억제작용가능여손해료ACh체질계통유관;응용GABAA수체조단제Bicuculline야사려대PS억제효응감약,표명려적억제작용야가능부분통과GABA도경기작용.
    BACKGROUND: As indicated by previous researches, aluminium (Al) could affect learning and memory of animals through many approaches in cluding affecting the stable status of intracellular calcium, decreasing protein kinase C(PKC) activity, and affecting the release of glutamic acid (Glu) . The formation of long-term potentiation(LTP) weakens in hip pocampal CA3 region of rats fed by forage containing Al. It could be found that Al would weaken evoked potential(EP) in hippocampal CA3 region and inhibit LTP formation, which might be related with the damaging effect of Al on L-Arg-NO approach through further application of acute Al administration, i.e., AlCl3 is directly injected into hippocampal CA3 region by microinjection.OBJECTIVE: To investigate the damaging effect of Al on learning and memory, and its correlation with cholinergic system and gamma-aminobutyric acid (GABA) system.DESIGN: A completelyrandomized controlled verifying study based on the experimental animals.SETTING: Department of psychology in a university and the medical college of an occupational technology college.MATERIALS: The study was conducted in the Laboratory of Neuro-Electrophysiology, the Faculty of Physiology, Tongji Medical College,Huazhong University of Science and Technology between September 2000 and April 2001. Totally 68 SD rats of ordinary grade in either gender with a body mass between 150 g and 250 g were obtained from the Department of Experimental Animals of Tongji Medical College, Huazhong University of Science and echnology.INTERVENTIONS: SD rats were randomly divided into 9 groups including normal NS ( NS ) control group ( n = 6): 1 μL of NS was injected twice ( 1 minute interval) into hippocampal CA3 region by microinjection; NS + AlCl3 group( n = 6): 1 μL of NS and 0.5 mol/L of AlCl3 were injected(1 minute interval) into hippocampal CA3 region by microinjection;NS + Tac group( n = 6): 1 μLof NS and 1 × 10-9 mol/L of Tacrine were injected in turn into hippocampal CA3 region by microinjection; NS + Bic group(n=6): 1 μL of NS and 1 × 10-3 mol/L of Bicuculline were injected in turn into hippocampal CA3 region by microinjection; Tac +AlCl3 group: 1 μL of 1 × 10-9 mol/L( n =8),1 × 10-10 mol/L ( n = 6) and 1 × 10-8 mol/L of Tacrine were firsdy injected into hippocampal CA3 region by microinjection, and 1 μL of 0. 5 mol/L AlCl3was injected 1 minute later; Bic + AlCl3 group: 1 μL of 1 × 10-3 mol/L( n = 9) and 1 × 10 -4 mol/L( n = 7) of Bicuculline were firstly injected into hippocampal CA3 region by microinjection, and 1 μL of 0.5 mol/L AlCl3 was injected 1 minute later. Population spike(PS) in hippocampal CA3 region was recorded after using single pulse to stimulate perforating fiber(PF). When PS became stable, medication was injected into hippocampal CA3 region to observe the impacts of Al on EP in hippocampal CA3 region and the impacts of some central transmitters on the effect of Al in in hibiting PS.MAIN OUTCOME MEASURES: PS evoked in hippocampal CA3 region;the impacts of Al on EP in CA3 region and the impacts of some central transmitters on the effect of Al in inhibiting PS. RESULTS: ① After the application of 0.5 mol/L of AlCl3 in hippocampal CA3 region by microinjection, the recorded amplitude of PS reduced to peak at 1 minute, which accounted for(33.8 ± 11. 0) % of the level before medication( n = 6). The inhibitive effect of AlCl3 lasted for 120 minutes. ② After the pre-application of 1 × 10-9 mol/L of Tacrine(cholinesterase in hibitor) into CA3 region by microinjection and the application of AlCl3 at one minute later, it was found that Tacrine antagonized the inhibitive effects of AlCl3 on PS within 1 to 30 minutes( n = 8) . Its antagonism would extend to 60 minutes if 1 × 10-8 mol/L of Tacrine was administrated( n = 6) . How ever, the antagonism of 1 × 10-10 mol/L of Tacrine was weaker than that of 1×10-9 mol/L group within 3-5 minutes(n=6) ③ After the pre-application of 1 × 10-3 mol/L of Bicuculline into CA3 region by mi croinjection and the application of AlCl3 at one minute later, Bicuculline could partially weaken the effects of AlCl3 within 1 to 20 minutes( n = 9). CONCLUSION: Al of certain concentration can inhibit the evoked PS am plitude in hippocampal CA3 region; Tacrine can antagonize Al' s effects and its antagonism might be related with dose. Hence, the inhibitive effects of Al might be related with the damage in Ach transmitter system. The application of Bicuculline, a GABAA inhibitor, also can weaken the PS inhibitive effects of Al, which indicates that the inhibitive effect of Al also might be effective through GABA approach.
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