背景:酸性肽是由3个谷氨酸连接而成的三肽,不可能像单个谷氨酸一样直接作为兴奋性神经递质而由突触前释放并与突触后的NMDA受体结合而发挥兴奋性神经信号传递作用,但通过与多种代谢性谷氨酸受体结合而促进神经细胞增殖或释放神经生长因子而发挥作用具有很大的可能性.目的:探讨酸性肽是否能够引起阿尔茨海默病模型大鼠学习记忆能力的变化.设计:随机对照单一实验.单位:郑州大学基础医学院生物化学与分子生物学教研室.材料:实验于2003-02/07在郑州大学基础医学院生物化学与分子生物学教研室的第二研究室和实验动物房完成.选取雄性SD大鼠100只,用跳台实验除去反应迟钝的动物,共84只大鼠纳入实验,随机分为7组:正常对照组,模型组,生理盐水组,吡拉西坦治疗组,酸性肽60,30,15 mg/kg治疗组,12只/组.酸性肽为本课题组从牛脑中分离出的一个新的小分子肽,由三个谷氨酸连成的三肽.方法:除正常对照组外,其余各组大鼠常规饲养1周后,均采用大鼠脑组织立体定位微量注射技术,脑海马注射5 μg鹅膏蕈氨酸,以损毁大鼠双侧迈纳特基底核建立阿尔茨海默病模型.正常对照组和模型组不给药,生理盐水组用生理盐水灌胃,吡拉西坦治疗组用0.3g/kg吡拉西坦灌胃,酸性肽60,30,15 mg/kg治疗组分别用60,30,15 mg/kg酸性肽灌胃,连续20 d,1次/d,2 mL/次.灌胃期满后通过跳台实验测定各组大鼠的学习和记忆能力.将动物放在跳台装置的安全台上,适应环境3 min,然后通以36 v电流,受到电击后动物跳至铜栅为错误反应,跳回安全区为正确反应,记录3 min内的上台潜伏期与正确反应次数.主要观测指标:各组大鼠学习与记忆能力的比较.结果:纳入实验的84只大鼠全部进入结果分析.①各组大鼠学习能力的比较:与模型组比较,酸性肽15,30,60 mg/kg治疗组的上台潜伏期均明显缩短[(102.03±5.33),(71.77±4.38),(68.28±9.53),(69.13±8.79)s,P＜0.01];正确反应次数均明显提高[(12.92±2.91),(16.17土2.79),(15.83±3.27),(16.33±2.53)次,P＜0.01].②各组大鼠记忆能力的比较:与模型组比较,酸性肽15,30,60mg/kg治疗组的上台潜伏期均明显缩短[(43.17±4.66),(29.78土4.48),(26.20±3.28),(22.09±4.43)s,P＜0.01];正确反应次数均明显提高[(15.67±2.15),(20.92土2.68),(20.83±2.29),(20.25±2.05)次,P＜0.01].结论:酸性肽能够明显缩短阿尔茨海默病鼠在跳台实验中的上台潜伏期,提高正确反应次数,表明酸性肽对阿尔茨海默病模型大鼠的学习记忆能力具有良好的于预作用.
揹景:痠性肽是由3箇穀氨痠連接而成的三肽,不可能像單箇穀氨痠一樣直接作為興奮性神經遞質而由突觸前釋放併與突觸後的NMDA受體結閤而髮揮興奮性神經信號傳遞作用,但通過與多種代謝性穀氨痠受體結閤而促進神經細胞增殖或釋放神經生長因子而髮揮作用具有很大的可能性.目的:探討痠性肽是否能夠引起阿爾茨海默病模型大鼠學習記憶能力的變化.設計:隨機對照單一實驗.單位:鄭州大學基礎醫學院生物化學與分子生物學教研室.材料:實驗于2003-02/07在鄭州大學基礎醫學院生物化學與分子生物學教研室的第二研究室和實驗動物房完成.選取雄性SD大鼠100隻,用跳檯實驗除去反應遲鈍的動物,共84隻大鼠納入實驗,隨機分為7組:正常對照組,模型組,生理鹽水組,吡拉西坦治療組,痠性肽60,30,15 mg/kg治療組,12隻/組.痠性肽為本課題組從牛腦中分離齣的一箇新的小分子肽,由三箇穀氨痠連成的三肽.方法:除正常對照組外,其餘各組大鼠常規飼養1週後,均採用大鼠腦組織立體定位微量註射技術,腦海馬註射5 μg鵝膏蕈氨痠,以損燬大鼠雙側邁納特基底覈建立阿爾茨海默病模型.正常對照組和模型組不給藥,生理鹽水組用生理鹽水灌胃,吡拉西坦治療組用0.3g/kg吡拉西坦灌胃,痠性肽60,30,15 mg/kg治療組分彆用60,30,15 mg/kg痠性肽灌胃,連續20 d,1次/d,2 mL/次.灌胃期滿後通過跳檯實驗測定各組大鼠的學習和記憶能力.將動物放在跳檯裝置的安全檯上,適應環境3 min,然後通以36 v電流,受到電擊後動物跳至銅柵為錯誤反應,跳迴安全區為正確反應,記錄3 min內的上檯潛伏期與正確反應次數.主要觀測指標:各組大鼠學習與記憶能力的比較.結果:納入實驗的84隻大鼠全部進入結果分析.①各組大鼠學習能力的比較:與模型組比較,痠性肽15,30,60 mg/kg治療組的上檯潛伏期均明顯縮短[(102.03±5.33),(71.77±4.38),(68.28±9.53),(69.13±8.79)s,P＜0.01];正確反應次數均明顯提高[(12.92±2.91),(16.17土2.79),(15.83±3.27),(16.33±2.53)次,P＜0.01].②各組大鼠記憶能力的比較:與模型組比較,痠性肽15,30,60mg/kg治療組的上檯潛伏期均明顯縮短[(43.17±4.66),(29.78土4.48),(26.20±3.28),(22.09±4.43)s,P＜0.01];正確反應次數均明顯提高[(15.67±2.15),(20.92土2.68),(20.83±2.29),(20.25±2.05)次,P＜0.01].結論:痠性肽能夠明顯縮短阿爾茨海默病鼠在跳檯實驗中的上檯潛伏期,提高正確反應次數,錶明痠性肽對阿爾茨海默病模型大鼠的學習記憶能力具有良好的于預作用.
배경:산성태시유3개곡안산련접이성적삼태,불가능상단개곡안산일양직접작위흥강성신경체질이유돌촉전석방병여돌촉후적NMDA수체결합이발휘흥강성신경신호전체작용,단통과여다충대사성곡안산수체결합이촉진신경세포증식혹석방신경생장인자이발휘작용구유흔대적가능성.목적:탐토산성태시부능구인기아이자해묵병모형대서학습기억능력적변화.설계:수궤대조단일실험.단위:정주대학기출의학원생물화학여분자생물학교연실.재료:실험우2003-02/07재정주대학기출의학원생물화학여분자생물학교연실적제이연구실화실험동물방완성.선취웅성SD대서100지,용도태실험제거반응지둔적동물,공84지대서납입실험,수궤분위7조:정상대조조,모형조,생리염수조,필랍서탄치료조,산성태60,30,15 mg/kg치료조,12지/조.산성태위본과제조종우뇌중분리출적일개신적소분자태,유삼개곡안산련성적삼태.방법:제정상대조조외,기여각조대서상규사양1주후,균채용대서뇌조직입체정위미량주사기술,뇌해마주사5 μg아고심안산,이손훼대서쌍측매납특기저핵건립아이자해묵병모형.정상대조조화모형조불급약,생리염수조용생리염수관위,필랍서탄치료조용0.3g/kg필랍서탄관위,산성태60,30,15 mg/kg치료조분별용60,30,15 mg/kg산성태관위,련속20 d,1차/d,2 mL/차.관위기만후통과도태실험측정각조대서적학습화기억능력.장동물방재도태장치적안전태상,괄응배경3 min,연후통이36 v전류,수도전격후동물도지동책위착오반응,도회안전구위정학반응,기록3 min내적상태잠복기여정학반응차수.주요관측지표:각조대서학습여기억능력적비교.결과:납입실험적84지대서전부진입결과분석.①각조대서학습능력적비교:여모형조비교,산성태15,30,60 mg/kg치료조적상태잠복기균명현축단[(102.03±5.33),(71.77±4.38),(68.28±9.53),(69.13±8.79)s,P＜0.01];정학반응차수균명현제고[(12.92±2.91),(16.17토2.79),(15.83±3.27),(16.33±2.53)차,P＜0.01].②각조대서기억능력적비교:여모형조비교,산성태15,30,60mg/kg치료조적상태잠복기균명현축단[(43.17±4.66),(29.78토4.48),(26.20±3.28),(22.09±4.43)s,P＜0.01];정학반응차수균명현제고[(15.67±2.15),(20.92토2.68),(20.83±2.29),(20.25±2.05)차,P＜0.01].결론:산성태능구명현축단아이자해묵병서재도태실험중적상태잠복기,제고정학반응차수,표명산성태대아이자해묵병모형대서적학습기억능력구유량호적우예작용.
BACKGROUND: Acidic peptide is the tripeptide composed of 3 glutamic acids, which cannot bring excitatory nerve signal transmission into play like single glutamic acid through presynaptic release and integration with postsynaptic NMDA receptor directly as excitable neurotransmitter. It is quite possible that acidic peptide plays its actions by integrating with multiple metabolic glutamic acidic receptors so as to promote neuron proliferation or release nerve growth factor (NGF). OBJECTIVE: To probe into whether acidic peptide induces changes in learning and memory of model rats with Alzheimer disease (AD).DESIGN: Randomized controlled single experiment was designed.SETTING: Teaching-Research Room of Biochemistry and Molecular Biology of Basic Medical College of Zhengzhou University.MATERIALS: The experiment was performed in 2nd Research Room and Experimental Animal Room of Teaching-Research Room of Biochemistry and Molecular Biology of Basic Medical College of Zhengzhou University.Totally 100 SD male rats were selected and some of them were excluded due to retarded response in step down test. Totally 84 rats were included in the experiment and randomized into 7 groups, named normal control,model group, physiological saline group (PS group), piracetam group, acidic peptide groups of 60, 30 and 15 mg/kg, 12 rats in each group. Acidic peptide is a new small molecular peptide separated from bovine brain in this research team and is tripeptide composed of three glutamic acids.METHODS: Except normal control, in the rest groups, after 1 week routine breeding, cerebral stereotactic microinjection was used to inject 5 μg ibotenic acid in hippocampus of rats to destroy bilateral Meynert's basal ganglia to establish AD model. In normal control and model group, no medication was applied. In PS group, physiological saline was used for gastric perfusion. In piracetam group, piracetam of 0.3 g/kg was used for gastric perfusion and in acidic peptide groups of 15, 30 and 60 mg/kg,acidic peptide of 60, 30 and 15 mg/kg was applied for gastric perfusion successively, continuously for 20 days, once per day, 2 mL/time. On the expiration of gastric perfusion, learning and memory of rats were examined with step down test in every group. The animal was placed on the safe table on step down platform to adapt to the environment for 3 minutes, afterwards, 36 V electric current was given. Error response was recorded if the animal jumped to the copper railings after electric shock and correct response was recorded if the animal jumped back the safe area. Step-up latent phase and frequency of correct response were recorded in 3 minutes.MAIN OUTCOME MEASURES: Comparison of learning and memory of rats in every group. RESULTS: Totally 84 rats were all included in the result analysis. ①Comparison of learning in every group: Compared with model group, stepup latent phase was shortened remarkably in every acidic peptide group[(102.03±5.33), (71.77±4.38), (68.28±9.53), (69.13±8.79) s, P ＜ 0.01] and the frequency of correct response was improved remarkably [(12.92±2.91),(16.17±2.79), (15.83±3.27), (16.33±2.53) times, P ＜ 0.01]. ② Comparison of memory in every group: Compared with model group, step-up latent phase was shortened remarkably in every acidic peptide group [(43.17±4.66),(29.78±4.48), (26.20±3.28), (22.09±4.43) s, P ＜ 0.01] and the frequency of correct response was improved remarkably [(15.67±2.15), (20.92±2.68),(20.83±2.29), (20.25±2.05) times, P ＜ 0.01].CONCLUSION: Acidic peptide can shorten remarkably the step-up latent phase of AD rats in step down test and improve the frequency of correct response. It is indicated that acidic peptide provides good intervention on learning and memory of rat model of Alzheimer disease.
