血管性痴呆大鼠海马DG区几种氨基酸含量的变化
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摘要
目的：本实验利用长期双侧颈总动脉结扎法制备血管性痴呆(Vascular dementi, VD)大鼠模型,并观察大鼠海马齿状回(Dentate gyrus, DG)区细胞外液中几种氨基酸含量的变化,探讨血管性痴呆对大鼠DG区氨基酸的影响。
方法：本实验将成年Wistar大鼠(250-300g)随机分成对照组(n=6)、假手术组(n=6)和模型组(VD组)(n=6)。对照组不做手术,假手术组只剥离双侧颈总动脉但是不结扎,模型组剥离并永久性结扎双侧颈总动脉。术后30天开始,采用Morris水迷宫进行学习记忆的行为学观察；训练结束后,利用脑内微量透析法和高效液相色谱法测定海马DG区细胞外液中的7种氨基酸类物质(包括天门冬氨酸、谷氨酰胺、谷氨酸、甘氨酸、牛磺酸、丙氨酸和γ-氨基丁酸)的含量。
结果：1.VD组与假手术组、对照组相比,水迷宫实验的逃避潜伏期明显延长,具有统计学意义(均为P<0.05),假手术组和对照组之间无明显差异(P>0.05)。2.VD组海马DG区细胞外液中的谷氨酰胺、牛磺酸、丙氨酸和γ-氨基丁酸的含量均明显高于对照组和假手术组,具有统计学意义(均为P<0.05)。其余三种氨基酸无明显变化(均为P>0.05)；假手术组的海马DG区七种氨基酸含量与对照组相比无明显差异(均为P>0.05)。
结论：1.采用双侧颈总动脉结扎术能有效制备VD模型;2.VD可能与海马DG区谷氨酰胺、牛磺酸、丙氨酸和γ-氨基丁酸含量增加有关。
Objective:To discussed the effect of vascular dementia on amino acids levels in hippocampal Dentate gyrus (DG) region, the vascular dementia (VD) rat model was prepared with permanent bilateral carotid artery ligation, and the extracellular concentrations of several amino acids in hippocampal DG region were observed in the VD rats.
Methods:Adult Wistar rats (250～300g) were randomly divided into control group (n=6), sham operation group (n=6) and model group (VD group) (n=6). Control group without operation, sham operation group only bilateral carotid artery dissection but not ligation, model group stripping and permanent bilateral carotid artery ligation.30 days after the surgery, learning and memory behavior were observed using Morris water maze; after training, the extracellular concentrations of several amino acids(including aspartic acid, glutamine, glutamic acid, glycine, taurine, alanine and y-aminobutyric acid) in hippocampal DG region were determined by using brain microdialysis and high performance liquid chromatography techniques.
Results:1. VD group compared with the sham group and the control group, water maze escape latency was prolonged, with statistical significance (P< 0.05, respectively), no significant difference between sham group and the control group (P > 0.05); 2. glutamine, taurine, alanine and y-aminobutyric acid levels were significantly higher than the control and the sham group, with statistical significance (P<0.05, respectively). No significant change in the other three amino acids (P> 0.05, respectively), and concentration of amino acids showed no significant difference between the control and the sham group (P> 0.05, respectively).
Conclusion:1. Bilateral carotid artery ligation could effectively prepare VD model; 2. VD may be associated with enhancing of glutamine, taurine, alanine and y-aminobutyric acid in hippocampal DG region.
方法：本实验将成年Wistar大鼠(250-300g)随机分成对照组(n=6)、假手术组(n=6)和模型组(VD组)(n=6)。对照组不做手术,假手术组只剥离双侧颈总动脉但是不结扎,模型组剥离并永久性结扎双侧颈总动脉。术后30天开始,采用Morris水迷宫进行学习记忆的行为学观察；训练结束后,利用脑内微量透析法和高效液相色谱法测定海马DG区细胞外液中的7种氨基酸类物质(包括天门冬氨酸、谷氨酰胺、谷氨酸、甘氨酸、牛磺酸、丙氨酸和γ-氨基丁酸)的含量。
结果：1.VD组与假手术组、对照组相比,水迷宫实验的逃避潜伏期明显延长,具有统计学意义(均为P<0.05),假手术组和对照组之间无明显差异(P>0.05)。2.VD组海马DG区细胞外液中的谷氨酰胺、牛磺酸、丙氨酸和γ-氨基丁酸的含量均明显高于对照组和假手术组,具有统计学意义(均为P<0.05)。其余三种氨基酸无明显变化(均为P>0.05)；假手术组的海马DG区七种氨基酸含量与对照组相比无明显差异(均为P>0.05)。
结论：1.采用双侧颈总动脉结扎术能有效制备VD模型;2.VD可能与海马DG区谷氨酰胺、牛磺酸、丙氨酸和γ-氨基丁酸含量增加有关。
Objective:To discussed the effect of vascular dementia on amino acids levels in hippocampal Dentate gyrus (DG) region, the vascular dementia (VD) rat model was prepared with permanent bilateral carotid artery ligation, and the extracellular concentrations of several amino acids in hippocampal DG region were observed in the VD rats.
Methods:Adult Wistar rats (250～300g) were randomly divided into control group (n=6), sham operation group (n=6) and model group (VD group) (n=6). Control group without operation, sham operation group only bilateral carotid artery dissection but not ligation, model group stripping and permanent bilateral carotid artery ligation.30 days after the surgery, learning and memory behavior were observed using Morris water maze; after training, the extracellular concentrations of several amino acids(including aspartic acid, glutamine, glutamic acid, glycine, taurine, alanine and y-aminobutyric acid) in hippocampal DG region were determined by using brain microdialysis and high performance liquid chromatography techniques.
Results:1. VD group compared with the sham group and the control group, water maze escape latency was prolonged, with statistical significance (P< 0.05, respectively), no significant difference between sham group and the control group (P > 0.05); 2. glutamine, taurine, alanine and y-aminobutyric acid levels were significantly higher than the control and the sham group, with statistical significance (P<0.05, respectively). No significant change in the other three amino acids (P> 0.05, respectively), and concentration of amino acids showed no significant difference between the control and the sham group (P> 0.05, respectively).
Conclusion:1. Bilateral carotid artery ligation could effectively prepare VD model; 2. VD may be associated with enhancing of glutamine, taurine, alanine and y-aminobutyric acid in hippocampal DG region.
引文
[1]肖桂芳.血管性痴呆的临床表现及药物治疗方案.中国社区医师·医学专业2010,9：3.
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[3]刘铮、包汉雨等.血管性痴呆及其治疗国外医学神经病学神经外科学分册2000,27(3)：143-145.
[4]邓雪珍,叶惠淑。血管性痴呆的发生率及相关因素。心血管康复医学杂志2002,11(2)：167-168.
[5]于国勤,徐旭日,侯小群.血管性痴呆与脑梗死病灶的关系.中国临床康复2004,8(1)：87.
[6]Eichenbaum H. The hippocampus and mechanism of declarative memory. Behav. Brain Res.1999,103:123-133.
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[9]Bashir ZI, Alford S., Davies SN, et al. Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus. Nature 1991,349:156-158.
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[12]Richter LG, Canevari L, Bliss TV. Long-term potentiation and glutamate release in the dentate gyrus:links to spatial learning. Behav Brain Res.1995,66:37-40.
[13]Qiao-feng Liu, Qing-hua Jin, Hai-ying Jiang, et al. Changer of amino acids in hippocampal dentate gyrus during learning-dependent long-term potentiation in free moving conscious rats. Chinese Journal of Clinical Rehabilitation 2006,10(38):71-35.
[14]孙志刚,姜岩,包金锁,等AMPA受体对清醒大鼠海马DG区学习记忆功能的影响.中华神经外科杂志2009,25(2)：182-184.
[15]张世仪.学习过程中脑内NO变化的研究.中国医学科学院学报1997,19(1)：17.
[16]Sorrentino G, Migliaccio R, et al. Treatment of vascular dementia: the route of prevention. European Neurology 2008,60:217-223.
[17]姜楠,王发渭.血管性痴呆的中医药实验研究进展与展望.时珍国医国药2002,13：379-380。
[18]张爱林,徐秋萍等.多发性脑梗塞痴呆动物模型评价.上海实验动物科学2003,23：186-188.
[19]郑敏,赵骥,陈红光,王帮华,鲍翠玉.大鼠血管性痴呆模型的改良.咸宁学院学报(医学版)2008,22(4)：277.
[20]Jin QH, Yuto Ueda, Yuta Ishizuka, et al. Cardiovascular changes induced by central hypertonic saline are accompanied by glutamate release in awake rats. Am J Physiol.2001,281:1224-1231.
[21]许世彤,易立等.NMDA受体在海马习得性长时程突触增强形成中的作用.心理学报,1991,1：74-79.
[22]Bon CLM, Garthwaite J, et al. On the role of nitric oxide in hippocampal long-term potentiation. J Neuroscience,2003,23: 1941-1948.
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[24]蔡晶,杜建.血管性痴呆动物模型的制作方法及其评价.中医药学刊,2002, 20(5)：617
[25]张留宝,陈进贵,刘平,等.不同动物的不同脑供血动脉结扎后存活率比较.南京军医学院学报,2002,24(2)：73
[26]Souba W, Herslowitz K, Austgen T, et al. Glutamine nutrition: theoretical considerations and therapeutic impact. JPEN,1990,14: 2375-2435.
[27]王尧,杜子威主编.神经生物化学与分子生物学.北京：人民卫生出版社,1997,197—207.
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[30]韩晓滨,刘冬生.牛磺酸与大脑发育关系的初步探讨—牛磺酸与行为[J]卫生研究,1988,17：22-26.
[1]Kee Hyung Park, Lee JY, Na DL, et al. Different associations of periventricularand deep white matter lesions with cognition, neuropsychiatric symptoms, and daily activities in dementia [J]. J Geriatr Psychiatry Neurol.2011; 24(2):84-90.
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[3]刘铮、包汉雨等.血管性痴呆及其治疗国外医学神经病学神经外科学分册2000,27(3)：143-145.
[4]邓雪珍,叶惠淑。血管性痴呆的发生率及相关因素。心血管康复医学杂志2002,11(2)：167-168.
[5]于国勤,徐旭日,侯小群.血管性痴呆与脑梗死病灶的关系.中国临床康复2004,8(1)：87.
[6]Eichenbaum H. The hippocampus and mechanism of declarative memory. Behav. Brain Res.1999,103:123-133.
[7]Fein G, DiSclafani V, et al. Hippocampal and corticalatrophy predict dementia in subcortical ischemic vascular disease Neurology, 2000,55:1626-35.
[8]Kril JJ, Patel S, et al. Patients with vascular dementia due to microvascular pathology have significant hippocampal neuronal loss J Neurol Neurosurg Psychiatry 2002,72:747-751.
[9]Bashir ZI, Alford S., Davies SN, et al. Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus. Nature 1991,349:156-158.
[10]梁发权,吕宝璋.老龄小鼠中枢兴奋性氨基酸递质及N-甲基-D-天冬氨酸受体的变化.中华医学杂志1992,72(1)：33-35.
[11]Bliss TV, Collingridge GL. A synaptic model of memory:long-term potentiation in the hippocampus.Nature 1993,361:31-39.
[12]Richter LG, Canevari L, Bliss TV. Long-term potentiation and glutamate release in the dentate gyrus:links to spatial learning. Behav Brain Res.1995,66:37-40.
[13]Qiao-feng Liu, Qing-hua Jin, Hai-ying Jiang, et al. Changer of amino acids in hippocampal dentate gyrus during learning-dependent long-term potentiation in free moving conscious rats. Chinese Journal of Clinical Rehabilitation 2006,10(38):71-35.
[14]孙志刚,姜岩,包金锁,等AMPA受体对清醒大鼠海马DG区学习记忆功能的影响.中华神经外科杂志2009,25(2)：182-184.
[15]张世仪.学习过程中脑内NO变化的研究.中国医学科学院学报1997,19(1)：17.
[16]Sorrentino G, Migliaccio R, et al. Treatment of vascular dementia: the route of prevention. European Neurology 2008,60:217-223.
[17]姜楠,王发渭.血管性痴呆的中医药实验研究进展与展望.时珍国医国药2002,13：379-380。
[18]张爱林,徐秋萍等.多发性脑梗塞痴呆动物模型评价.上海实验动物科学2003,23：186-188.
[19]郑敏,赵骥,陈红光,王帮华,鲍翠玉.大鼠血管性痴呆模型的改良.咸宁学院学报(医学版)2008,22(4)：277.
[20]Jin QH, Yuto Ueda, Yuta Ishizuka, et al. Cardiovascular changes induced by central hypertonic saline are accompanied by glutamate release in awake rats. Am J Physiol.2001,281:1224-1231.
[21]许世彤,易立等.NMDA受体在海马习得性长时程突触增强形成中的作用.心理学报,1991,1：74-79.
[22]Bon CLM, Garthwaite J, et al. On the role of nitric oxide in hippocampal long-term potentiation. J Neuroscience,2003,23: 1941-1948.
[23]韩晓滨,刘冬生.牛磺酸与大脑发育关系的初步探讨—牛磺酸与行为.卫生研究,1988,17：22-26.
[24]蔡晶,杜建.血管性痴呆动物模型的制作方法及其评价.中医药学刊,2002, 20(5)：617
[25]张留宝,陈进贵,刘平,等.不同动物的不同脑供血动脉结扎后存活率比较.南京军医学院学报,2002,24(2)：73
[26]Souba W, Herslowitz K, Austgen T, et al. Glutamine nutrition: theoretical considerations and therapeutic impact. JPEN,1990,14: 2375-2435.
[27]王尧,杜子威主编.神经生物化学与分子生物学.北京：人民卫生出版社,1997,197—207.
[28]韩晓滨.牛磺酸对人脑神经细胞增殖分化影响的研究[J].生理科学进展,1992,23：399-341.
[29]张在香,沈方兰,李玉声.牛磺酸对体外培养人胚脑神经细胞生长发育和衰老的影响[J].营养学,1996,18：386-391.
[30]韩晓滨,刘冬生.牛磺酸与大脑发育关系的初步探讨—牛磺酸与行为[J]卫生研究,1988,17：22-26.
[1]Kee Hyung Park, Lee JY, Na DL, et al. Different associations of periventricularand deep white matter lesions with cognition, neuropsychiatric symptoms, and daily activities in dementia [J]. J Geriatr Psychiatry Neurol.2011; 24(2):84-90.
[2]贾建平,王树英。血管性痴呆临床诊断标准探讨[J]。中国神经免疫学和神经病学杂志,2010,17(6)：387-389.
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