当归多糖对阿尔茨海默病模型大鼠学习记忆及β-淀粉样蛋白代谢的影响
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摘要
目的观察当归多糖对阿尔茨海默病(AD)模型大鼠学习记忆、海马β-淀粉样蛋白前体(APP)、β-淀粉样蛋白(Aβ)1-42及血清乙酰胆碱(Ach)、胆碱乙酰转移酶(ChAT)、乙酰胆碱酯酶(AChE)、超氧化物歧化酶(SOD)、丙二醛(MDA)的影响,探讨其防治AD的作用机制。方法 70只SPF级Wistar大鼠经水迷宫学习记忆能力筛选合格后,随机选取10只大鼠(雌雄各半)为假手术组,其余大鼠以脑立体定位注射Aβ25-35复制AD大鼠模型,以水迷宫学习记忆能力筛选造模成功的50只大鼠随机分为模型组、阳性药组和当归多糖低、中、高剂量组,每组10只。模型组和假手术组大鼠给予生理盐水灌胃,各给药组大鼠给予相应药液灌胃,每日给药体积均为2 m L/100 g,连续28 d。给药25~28 d Morris水迷宫测试大鼠学习记忆能力,然后取材检测血清Ach、ChAT、AChE、SOD、MDA及海马APP、Aβ1-42。结果与假手术组比较,模型组大鼠定位航行实验逃避潜伏期明显延长,目标象限滞留时间缩短,空间探索实验首次到达原逃生平台位置潜伏时间延长,穿越原平台位置及目标象限滞留的时间缩短,血清Ach含量与ChAT、SOD活性明显降低,AChE活性及MDA水平明显升高,海马APP、Aβ1-42含量升高,差异均有统计学意义(P<0.05,P<0.01);与模型组比较,各给药组大鼠逃避潜伏期均不同程度缩短,目标象限滞留时间延长,首次到达原逃生平台位置潜伏时间缩短,跨原平台次数增加,血清Ach含量和ChAT、SOD活性升高,AChE活性及MDA水平明降低,海马APP、Aβ1-42含量降低,差异均有统计学意义(P<0.05,P<0.01)。结论当归多糖可能通过改善胆碱能神经递质、提高抗自由基氧化能力及促进Aβ的代谢,改善AD模型大鼠学习记忆能力,对AD有一定的防治作用。
Objective To investigate effects of angelica polysaccharide on learning and memory abilities, Ach, ChAT, AChE, SOD, MDA in serum, APP and Aβ1-42 in hippocampus in model rats with Alzheimer disease(AD); To explore the mechanism of angelica polysaccharide for the treatment of AD. Methods Seventy SPF Wistar rats were selected for learning and memory ability by water maze. 10 rats were randomly selected(half female and half male) as sham-operation group, and the others were injected with Aβ25-35 by stereotatic techniques, copying AD model rats. 50 rats for learning and memory ability by water maze were successfully divided into model group, positive group, angelica polysaccharide low-, medium-, and high-dose groups, with 10 rats in each group. Rats in model group and sham-operation group were given normal saline for gavage, while rats in medication groups were given relevant medicine for gavage, 2 m L/(100 g·d), for 28 d. The learning and memory ability of rats in each group was tested by Morris water maze during 25-28 days, and the contents of Ach, ChAT, AChE, SOD, MDA in serum and APP and Aβ1-42 in hippocampus were determined. Results Compared with the sham-operation group, the escape latent period of model group was significantly prolonged in place navigation experiment; the target quadrant time was shortened; the latent time for the first time to reach the original escape platform was longer in spatial probe test; the residence time of crossing the original platform position and the target quadrant was shorter; the levels of Ach, the activity of ChAT and SOD in serum decreased; the levels of MDA, the activity of AChE in serum increased; the levels of APP and Aβ1-42 in hippocampus increased, with statistical significance(P<0.05, P<0.01). Compared with model group, the escape latent period of each medication group was shortened in different degrees after the intervention treatment; the residence time of target quadrant was prolonged; the latent time for the first time to reach the original escape platform was shortened; the number of cross platform increased; the levels of Ach, the activity of ChAT and SOD in serum increased; the levels of MDA and the activity of AChE in serum decreased; the levels of APP and Aβ1-42 in hippocampus significantly decreased, with statistical significance(P<0.05, P<0.01). Conclusion Angelica polysaccharide may effectively improve the learning and memory of ability of AD model rats to improve anti-free radical oxidation and promote Aβ metabolism and promote learning and memory ability of AD model rats, which have some preventive and therapeutic effects on AD.
Objective To investigate effects of angelica polysaccharide on learning and memory abilities, Ach, ChAT, AChE, SOD, MDA in serum, APP and Aβ1-42 in hippocampus in model rats with Alzheimer disease(AD); To explore the mechanism of angelica polysaccharide for the treatment of AD. Methods Seventy SPF Wistar rats were selected for learning and memory ability by water maze. 10 rats were randomly selected(half female and half male) as sham-operation group, and the others were injected with Aβ25-35 by stereotatic techniques, copying AD model rats. 50 rats for learning and memory ability by water maze were successfully divided into model group, positive group, angelica polysaccharide low-, medium-, and high-dose groups, with 10 rats in each group. Rats in model group and sham-operation group were given normal saline for gavage, while rats in medication groups were given relevant medicine for gavage, 2 m L/(100 g·d), for 28 d. The learning and memory ability of rats in each group was tested by Morris water maze during 25-28 days, and the contents of Ach, ChAT, AChE, SOD, MDA in serum and APP and Aβ1-42 in hippocampus were determined. Results Compared with the sham-operation group, the escape latent period of model group was significantly prolonged in place navigation experiment; the target quadrant time was shortened; the latent time for the first time to reach the original escape platform was longer in spatial probe test; the residence time of crossing the original platform position and the target quadrant was shorter; the levels of Ach, the activity of ChAT and SOD in serum decreased; the levels of MDA, the activity of AChE in serum increased; the levels of APP and Aβ1-42 in hippocampus increased, with statistical significance(P<0.05, P<0.01). Compared with model group, the escape latent period of each medication group was shortened in different degrees after the intervention treatment; the residence time of target quadrant was prolonged; the latent time for the first time to reach the original escape platform was shortened; the number of cross platform increased; the levels of Ach, the activity of ChAT and SOD in serum increased; the levels of MDA and the activity of AChE in serum decreased; the levels of APP and Aβ1-42 in hippocampus significantly decreased, with statistical significance(P<0.05, P<0.01). Conclusion Angelica polysaccharide may effectively improve the learning and memory of ability of AD model rats to improve anti-free radical oxidation and promote Aβ metabolism and promote learning and memory ability of AD model rats, which have some preventive and therapeutic effects on AD.
引文
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[12]王虎平,吴红彦.逍遥散对阿尔茨海默病模型小鼠血清及脑组织匀浆中SOD、GSH-Px活性及MDA水平的影响[J].甘肃中医学院学报,2013,30(6):1-3.
[13]吴红彦,李海龙,张云,等.黑逍遥散对东莨菪碱致痴呆小鼠模型的影响[J].中国中医药信息杂志,2013,20(10):35-37.
[14]BALARAMAN Y,LIMAYE A R,LEVEY A I.Glycogen synthase kinase3 beta and Alzheimer's disease:pathophysiological and therapeutic significance[J].Cell Mol Life Sci,2006,63(11):1226-1235.
[15]陈红,赵鹏,孙亚平.阿尔茨海默病发病机制研究进展[J].生物技术世界,2015,31(10):99-100.
[2]杨植媛,吴红彦,李海龙,等.当归含药血清对阿尔兹海默病细胞模型损伤的保护作用[J].辽宁中医杂志,2014,41(1):164-167.
[3]PAXINOS G,WATSON C.The rat brain in stereotaxic coordinates[M].5th ed.San Diego:Elsevier Academic Press,2005:82-84,114-116.
[4]李檬.老年期痴呆发病机制研究进展及预防对策[J].海军医学杂志,2005,26(1):81-82.
[5]BALLARD C,GAUTHIER S,CORBETT A,et al.Alzheimer's disease[J].Lancet,2011,377(9770):1019-1031.
[6]WEUVE J,PUETT R C,HWARTZ J,et al.Exposure to partculate air pollutionand cognitive decline in older women[J].Air Intern Med,2012,172(3):219-227.
[7]POWER M C,WEISSKOPF M G,ALEXEEFF S E,et al.Traffic related air pollutionand cognitive function in a cohort of older men[J].Environ Health Perspec,2011,119(5):682-687.
[8]李浩,高普.实用老年疾病诊断与治疗[M].北京:科学技术文献出版社,2000:656-667.
[9]BAMBERGER M E,HARRIS M E,MC DONALD D R.A cell surface receptor complex for fibrillar beta-amyloid mediates microglial activation[J].J Neurosci,2003,23(7):2665-2674.
[10]PIMPLIKAR S W.Reassessing the amyloid cascade hypothesis of Alzheimer's disease[J].Int J Biochem Cell Biol,2009,41(6):1261-1268.
[11]吴红彦,王虎平.以肝脾论治老年性痴呆及逍遥散对老年痴呆模型小鼠学习记忆能力、中枢胆碱能神经元活性的影响[J].中国实验方剂学杂志,2010,16(5):168-170.
[12]王虎平,吴红彦.逍遥散对阿尔茨海默病模型小鼠血清及脑组织匀浆中SOD、GSH-Px活性及MDA水平的影响[J].甘肃中医学院学报,2013,30(6):1-3.
[13]吴红彦,李海龙,张云,等.黑逍遥散对东莨菪碱致痴呆小鼠模型的影响[J].中国中医药信息杂志,2013,20(10):35-37.
[14]BALARAMAN Y,LIMAYE A R,LEVEY A I.Glycogen synthase kinase3 beta and Alzheimer's disease:pathophysiological and therapeutic significance[J].Cell Mol Life Sci,2006,63(11):1226-1235.
[15]陈红,赵鹏,孙亚平.阿尔茨海默病发病机制研究进展[J].生物技术世界,2015,31(10):99-100.