普仑司特对东莨菪碱诱导的小鼠学习记忆损害的影响
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摘要
目的研究普仑司特对东莨菪碱诱导小鼠学习记忆损害的影响及其作用机制。方法采用连续腹腔注射东莨菪碱(0.8 mg·kg-1·d-1)诱导小鼠学习记忆损害模型,灌胃给予普仑司特(0.3,0.6,1.2 mg·kg-1·d-1),14 d后用Morris水迷宫和Y迷宫实验评价学习记忆功能,并测定脑内乙酰胆碱(Ach)、乙酰胆碱酯酶(Ach E)水平。结果普仑司特(0.3~1.2 mg·kg-1·d-1)能显著缩短小鼠在隐藏平台实验中寻找平台的潜伏期,增加空间探索实验中在原平台所在象限的停留时间和穿越原平台所在位置的次数,增加Y迷宫测试中正确反应次数。普仑司特还能显著增加小鼠脑组织海马区和皮层区Ach含量,并降低Ach E活性。结论普仑司特通过降低脑内Ach E活性,提高Ach含量,改善东莨菪碱诱导的小鼠学习记忆损害。
OBJECTIVE To investigate the effects of pranlukast on memory impairment induced by scopolamine in mice and its underlying mechanisms. METHODS Pranlukast(0.3, 0.6, 1.2 mg·kg-1·d-1) was orally administered 0.5 h after intraperitoneal injection with scopolamine(0.8 mg·kg-1·d-1) for consecutive 14 days. Memory function was evaluated by Morris water maze and Y maze tests. Changes in cholinergic system reactivity were also examined by measuring the acetylcholine(Ach) and acetylcholinesterase(Ach E) in the hippocampus and cortex. RESULTS Treatment with pranlukast(0.3-1.2 mg·kg-1·d-1) significantly decreased the escape latency in hidden platform test and increased the time spent in the platform quadrant and the number of platform location crossings in the spatial probe test, and increased the correct number in Y maze test. Pranlukast also significantly increased Ach level and decreased Ach E activity in the hippocampus and cortex. CONCLUSION Pranlukast may improve scopolamine-induced memory impairment through elevation of brain Ach levels resulting from inhibition of Ach E activity in mice.
OBJECTIVE To investigate the effects of pranlukast on memory impairment induced by scopolamine in mice and its underlying mechanisms. METHODS Pranlukast(0.3, 0.6, 1.2 mg·kg-1·d-1) was orally administered 0.5 h after intraperitoneal injection with scopolamine(0.8 mg·kg-1·d-1) for consecutive 14 days. Memory function was evaluated by Morris water maze and Y maze tests. Changes in cholinergic system reactivity were also examined by measuring the acetylcholine(Ach) and acetylcholinesterase(Ach E) in the hippocampus and cortex. RESULTS Treatment with pranlukast(0.3-1.2 mg·kg-1·d-1) significantly decreased the escape latency in hidden platform test and increased the time spent in the platform quadrant and the number of platform location crossings in the spatial probe test, and increased the correct number in Y maze test. Pranlukast also significantly increased Ach level and decreased Ach E activity in the hippocampus and cortex. CONCLUSION Pranlukast may improve scopolamine-induced memory impairment through elevation of brain Ach levels resulting from inhibition of Ach E activity in mice.
引文
[1]B?CK M,DAHLéN S E,DRAZEN J M,et al.International Union of Basic and Clinical Pharmacology.LXXXIV:leukotriene receptor nomenclature,distribution,and pathophysiological functions[J].Pharmacol Rev,2011,63(3):539-584.
[2]YU G L,WEI E Q,WANG M L,et al.Pranlukast,a cysteinyl leukotriene receptor-1 antagonist,protects against chronic ischemic brain injury and inhibits the glial scar formation in mice[J].Brain Res,2005,1053(1/2):116-125.
[3]QIAN X D,WEI E Q,ZHANG L,et al.Pranlukast,a cysteinyl leukotriene receptor 1 antagonist,protects mice against brain cold injury[J].Eur J Pharmacol,2006,549(1-3):35-40.
[4]WANG L,DU C,LV J,et al.Antiasthmatic drugs targeting the cysteinyl leukotriene receptor 1 alleviate central nervous system inflammatory cell infiltration and pathogenesis of experimental autoimmune encephalomyelitis[J].J Immunol,2011,187(5):2336-2345.
[5]TANG S S,HONG H,CHEN L,et al.Involvement of cysteinyl leukotriene receptor 1 in Aβ1-42-induced neurotoxicity in vitro and in vivo[J].Neurobiol Aging,2014,35(3):590-599.
[6]TANG S S,JI M J,CHEN L,et al.Protective effect of pranlukast on Aβ1-42-induced cognitive deficits associated with downregulation of cysteinyl leukotriene receptor 1[J].Int J Neuropsychopharmacol,2014,17(4):581-592.
[7]YANG S Y,CHEN W H,JIN H Z,et al.Dexmedetomidine prevents sevoflurane neurotoxicity via ERK1/2 MAPK signaling in the developing brain[J].Chin J Mod Appl Pharm(中国现代应用药学),2014,31(5):523-528.
[8]PERRY E,WALKER M,GRACE J,et al.Acetylcholine in mind:a neurotransmitter correlate of consciousness[J].Trends Neurosci,1999,22(6):273-280.
[9]DESMARAIS J E,GAUTHIER S.Alzheimer disease:clinical use of cholinergic drugs in Alzheimer disease[J].Nat Rev Neurol,2010,6(8):418-420.
[10]XIANG G Q,TANG S S,JIANG L Y,et al.PPARγagonist pioglitazone improves scopolamine-induced memory impairment in mice[J].J Pharm Pharmacol,2012,64(4):589-596.
[11]KOPELMAN M D,CORN T H.Cholinergic‘blockade’as a model for cholinergic depletion.A comparison of thememory deficits with those of Alzheimer-type dementia and the alcoholic Korsakoff syndrome[J].Brain Res,1988,111(Pt 5):1079-1110.
[2]YU G L,WEI E Q,WANG M L,et al.Pranlukast,a cysteinyl leukotriene receptor-1 antagonist,protects against chronic ischemic brain injury and inhibits the glial scar formation in mice[J].Brain Res,2005,1053(1/2):116-125.
[3]QIAN X D,WEI E Q,ZHANG L,et al.Pranlukast,a cysteinyl leukotriene receptor 1 antagonist,protects mice against brain cold injury[J].Eur J Pharmacol,2006,549(1-3):35-40.
[4]WANG L,DU C,LV J,et al.Antiasthmatic drugs targeting the cysteinyl leukotriene receptor 1 alleviate central nervous system inflammatory cell infiltration and pathogenesis of experimental autoimmune encephalomyelitis[J].J Immunol,2011,187(5):2336-2345.
[5]TANG S S,HONG H,CHEN L,et al.Involvement of cysteinyl leukotriene receptor 1 in Aβ1-42-induced neurotoxicity in vitro and in vivo[J].Neurobiol Aging,2014,35(3):590-599.
[6]TANG S S,JI M J,CHEN L,et al.Protective effect of pranlukast on Aβ1-42-induced cognitive deficits associated with downregulation of cysteinyl leukotriene receptor 1[J].Int J Neuropsychopharmacol,2014,17(4):581-592.
[7]YANG S Y,CHEN W H,JIN H Z,et al.Dexmedetomidine prevents sevoflurane neurotoxicity via ERK1/2 MAPK signaling in the developing brain[J].Chin J Mod Appl Pharm(中国现代应用药学),2014,31(5):523-528.
[8]PERRY E,WALKER M,GRACE J,et al.Acetylcholine in mind:a neurotransmitter correlate of consciousness[J].Trends Neurosci,1999,22(6):273-280.
[9]DESMARAIS J E,GAUTHIER S.Alzheimer disease:clinical use of cholinergic drugs in Alzheimer disease[J].Nat Rev Neurol,2010,6(8):418-420.
[10]XIANG G Q,TANG S S,JIANG L Y,et al.PPARγagonist pioglitazone improves scopolamine-induced memory impairment in mice[J].J Pharm Pharmacol,2012,64(4):589-596.
[11]KOPELMAN M D,CORN T H.Cholinergic‘blockade’as a model for cholinergic depletion.A comparison of thememory deficits with those of Alzheimer-type dementia and the alcoholic Korsakoff syndrome[J].Brain Res,1988,111(Pt 5):1079-1110.