涤痰汤对冈田酸诱导的阿尔茨海默病模型大鼠行为学影响及其机制的研究
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摘要
目的探讨涤痰汤干预阿尔茨海默病(Alzheimer’s disease, AD)模型大鼠的效果及机制。方法通过对Sprague Dawley大鼠双侧海马注射冈田酸(okadaic acid, OA)复制AD大鼠模型,用涤痰汤水煎液[1 g/100g/d]灌胃,3周后利用Morris水迷宫和Western blotting分别检测AD模型大鼠空间学习记忆能力和tau、PP2Ac蛋白磷酸化水平的变化。结果涤痰汤干预后能显著逆转OA诱导的大鼠AD样学习记忆能力减退,并能明显减轻OA诱导的tau蛋白Ser214、Ser262位点以及PP2Ac Tyr307位点的过度磷酸化。结论涤痰汤可逆转OA引起的AD样模型大鼠的学习记忆能力衰退,其机制可能与激活PP2A从而减轻tau蛋白的过度磷酸化有关。
引文
[1] 王平,张六通,邱幸凡.老年痴呆发病机制探讨[J].陕西中医,2001,22(8):479.
[2] 刘玲,李艳,姜幼明,等.涤痰汤对阿尔茨海默病模型大鼠行为学影响的实验研究[J].现代中西医结合杂志,2010,19(25):3154.
[3] Morris R. Developments of a water-maze procedure for studying spatial learning in the rat[J]. J Neurosci Methods, 1984, 11:47.
[4] Iqbal K, Grundke-Iqbal I, Smith AJ, et al. Identification and localization of a tau peptide to paired helical fi laments of Alzheimer disease[J]. Proc Natl Acad Sci U S A, 1989, 86:5646.
[5] Ramsden M, Kotilinek L, Forster C, et al. Age-dependent neurofi brillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L) [J]. J Neurosci, 2005, 25:10637.
[6] Liu F, Liang Z, Gong CX. Hyperphosphorylation of tau and protein phosphatases in Alzheimer disease[J]. Panminerva Med, 2006, 48:97.
[7] Stephan A, Laroche S, Davis S. Generation of aggregated beta-amyloid in the rat hippocampus impairs synaptic transmission and plasticity and causes memory deficits[J]. J Neurosci, 2001, 21:5703.
[8] Gong CX, Lidsky T, Wegiel J, et al. Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer’s disease[J]. J Biol Chem, 2000, 275:5535.
[9] Pei JJ, Sersen E, Iqbal K, et al. Expression of protein phosphatases (PP-1, PP-2A, PP-2B and PTP-1B) and protein kinases (MAP kinase and P34cdc2) in the hippocampus of patients with Alzheimer disease and normal aged individuals[J]. Brain Res, 1994, 655:70.
[10] Gong CX, Shaikh S,Wang JZ, et al. Phosphatase activity toward abnormally phosphorylated tau: decrease in Alzheimer disease brain[J]. J Neurochem, 1995, 65:732.
[11] Favre B, Turowski P, Hemmings BA. Differential inhibition and posttranslational modification of protein phosphatase 1 and 2A in MCF7 cells treated with calyculin-A, okadaic acid, and tautomycin[J]. J Biol Chem, 1997, 272:13856.
[12] Yin YY, Liu H, Cong XB,et al. Acetyl-L-Carnitine Attenuates Okadaic Acid Induced Tau Hyperphosphorylation and Spatial Memory Impairment in Rats[J]. J Alzheimer’s Dis, 2010, 19:735.
[13] 游秋云,王平,张茂林,等.固本化痰健脑方对阿尔茨海默氏病大鼠行为学的影响[J].湖北中医杂志,2005,27(3):9.
[14] 王平,刘玲,张六通.加味温胆汤对SAM-P/10老化痴呆鼠三个脑区递质氨基酸的影响[J].中国实验方剂学杂志,2001,7(4):24.
[15] 王跃伟,王峰,张业伟,等.补肾活血化痰法对血管性痴呆大鼠SOD、MDA的影响[J].中西医结合心脑血管杂志,2003,1(1):10..
[16] 杜曦.涤痰化瘀汤治疗老年痴呆38例临床观察[J].浙江中医学院学报,1995,19(1):25.
[2] 刘玲,李艳,姜幼明,等.涤痰汤对阿尔茨海默病模型大鼠行为学影响的实验研究[J].现代中西医结合杂志,2010,19(25):3154.
[3] Morris R. Developments of a water-maze procedure for studying spatial learning in the rat[J]. J Neurosci Methods, 1984, 11:47.
[4] Iqbal K, Grundke-Iqbal I, Smith AJ, et al. Identification and localization of a tau peptide to paired helical fi laments of Alzheimer disease[J]. Proc Natl Acad Sci U S A, 1989, 86:5646.
[5] Ramsden M, Kotilinek L, Forster C, et al. Age-dependent neurofi brillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L) [J]. J Neurosci, 2005, 25:10637.
[6] Liu F, Liang Z, Gong CX. Hyperphosphorylation of tau and protein phosphatases in Alzheimer disease[J]. Panminerva Med, 2006, 48:97.
[7] Stephan A, Laroche S, Davis S. Generation of aggregated beta-amyloid in the rat hippocampus impairs synaptic transmission and plasticity and causes memory deficits[J]. J Neurosci, 2001, 21:5703.
[8] Gong CX, Lidsky T, Wegiel J, et al. Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer’s disease[J]. J Biol Chem, 2000, 275:5535.
[9] Pei JJ, Sersen E, Iqbal K, et al. Expression of protein phosphatases (PP-1, PP-2A, PP-2B and PTP-1B) and protein kinases (MAP kinase and P34cdc2) in the hippocampus of patients with Alzheimer disease and normal aged individuals[J]. Brain Res, 1994, 655:70.
[10] Gong CX, Shaikh S,Wang JZ, et al. Phosphatase activity toward abnormally phosphorylated tau: decrease in Alzheimer disease brain[J]. J Neurochem, 1995, 65:732.
[11] Favre B, Turowski P, Hemmings BA. Differential inhibition and posttranslational modification of protein phosphatase 1 and 2A in MCF7 cells treated with calyculin-A, okadaic acid, and tautomycin[J]. J Biol Chem, 1997, 272:13856.
[12] Yin YY, Liu H, Cong XB,et al. Acetyl-L-Carnitine Attenuates Okadaic Acid Induced Tau Hyperphosphorylation and Spatial Memory Impairment in Rats[J]. J Alzheimer’s Dis, 2010, 19:735.
[13] 游秋云,王平,张茂林,等.固本化痰健脑方对阿尔茨海默氏病大鼠行为学的影响[J].湖北中医杂志,2005,27(3):9.
[14] 王平,刘玲,张六通.加味温胆汤对SAM-P/10老化痴呆鼠三个脑区递质氨基酸的影响[J].中国实验方剂学杂志,2001,7(4):24.
[15] 王跃伟,王峰,张业伟,等.补肾活血化痰法对血管性痴呆大鼠SOD、MDA的影响[J].中西医结合心脑血管杂志,2003,1(1):10..
[16] 杜曦.涤痰化瘀汤治疗老年痴呆38例临床观察[J].浙江中医学院学报,1995,19(1):25.