质子泵抑制剂引起阿尔茨海默病发病机制的研究进展
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摘要
质子泵抑制剂(PPIs)是H~+K~+-ATP酶抑制剂,是当前应用最多的一类酸抑制药物,PPIs作用于胃黏膜上的质子泵,抑制H~+的分泌,直接抑制胃酸产生。随着PPIs的应用越来越多,各种不良反应的报道也越来越多,且PPIs在老年人中的应用中存在疗程过长和适应症不适宜的问题。最新研究发现PPIs在老年患者中的使用可能会增加阿尔茨海默病的发生,综述了PPIs引起阿尔茨海默病发生的机制。
Proton pump inhibitors(PPIs) are H~+K~+-ATP inhibitors. They are currently the most populor acid-inhibitory drugs. They directly act on the proton pump of gastric mucosa by inhibiting the secretion of H~+ and inhibiting the production of gastric acid. With the growth of application of PPIs, a variety of adverse reactions occurs. At present, the main problems of PPIs are its overuse and the errors in the therapeutic indication, especially in the elderly people. The latest literature demonstrated that long-term use of PPIs can increase the adverse effects of Alzheimer's disease. Research progress on mechanism of PPIs causing Alzheimer's disease are reviewed in this paper.
Proton pump inhibitors(PPIs) are H~+K~+-ATP inhibitors. They are currently the most populor acid-inhibitory drugs. They directly act on the proton pump of gastric mucosa by inhibiting the secretion of H~+ and inhibiting the production of gastric acid. With the growth of application of PPIs, a variety of adverse reactions occurs. At present, the main problems of PPIs are its overuse and the errors in the therapeutic indication, especially in the elderly people. The latest literature demonstrated that long-term use of PPIs can increase the adverse effects of Alzheimer's disease. Research progress on mechanism of PPIs causing Alzheimer's disease are reviewed in this paper.
引文
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[18]Taipale H,Tolppanen A M,Tiihonen M,et al.No association between proton pump inhibitor use and risk of Alzheimer's disease[J].Am J Gastroenterol,2017,112(12):1802-1808.
[19]Hooshmand B,Solomon A,K?reholt I,et al.Homocysteine and holotranscobalamin and the risk of Alzheimer disease:a longitudinal study[J].Neurology,2010,75(16):1408-1414.
[20]Badiola N,Alcalde V,Pujol A,et al.The proton-pump inhibitor lansoprazole enhances amyloid beta production[J].PLo S One,2013,8(3):e58837.
[21]Maes M L,Fixen D R,Linnebur S A.Adverse effects of proton-pump inhibitor use in older adults:a review of the evidence[J].Ther Adv Drug Saf,2017,8(9):273-297.
[22]Fallahzadeh M K,Borhani Haghighi A,Namazi M R.Proton pump inhibitors:predisposers to Alzheimer disease?[J].J Clin Pharm Ther,2010,35(2):125-126.
[23]Majumdar A,Cruz D,Asamoah N,et al.Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils[J].Mol Biol Cell,2007,18(4):1490-1496.
[24]Namazi M R,Jowkar F.A succinct review of the general and immunological pharmacologic effects of proton pump inhibitors[J].J Clin Pharm Ther,2008,33(3):215-217.
[25]Spires-Jones T L,Meyer-Luehmann M,Osetek J D,et al.Impaired spine stability underlies plaque-related spine loss in an Alzheimer's disease mouse model[J].Am J Pathol,2007,171(4):1304-1311.
[26]Gong Y,Chang L,Viola K L,et al.Alzheimer's disease-affected brain:presence of oligomeric A beta ligands(ADDLs)suggests a molecular basis for reversible memory loss[J].Proc Natl Acad Sci U S A.2003,100(18):10417-10422.
[27]Haass C,Selkoe D J.Soluble protein oligomers in neurodegeneration:lessons from the Alzheimer's amyloid beta-peptide[J].Nat Rev Mol Cell Biol,2007,8(2):101-112.
[28]Gandy S.The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease[J].J Clin Invest,2005,115(5):1121-1129.
[29]Lam J R,Schneider J L,Zhao W,et al.Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency[J].JAMA,2013,310(22):2435-2442.
[30]Reynolds E.Vitamin B12,folic acid,and the nervous system[J].Lancet Neurol,2006,5(11):949-960.
[31]McCracken C,Hudson P,Ellis R,et al.Methylmalonic acid and cognitive function in the Medical Research Council Cognitive Function and Ageing Study[J].Am JClin Nutr,2006,84(6):1406-1411.
[32]Smith A D,Refsum H,Bottiglieri T,et al.Homocysteine and dementia:an international consensus statement[J].J Alzheimers Dis,2018,62(2):561-570.
[33]Christine C W,Auinger P,Joslin A,et al.Vitamin B12and homocysteine levels predict different outcomes in early Parkinson's disease[J].Mov Disord,2018,33(5):762-770.
[34]Banack S A,Caller T A,Stommel E W.The cyanobacteria derived toxin Beta-N-methylamino-L-alanine and amyotrophic lateral sclerosis[J].Toxins(Basel),2010,2(12):2837-2850.
[35]Ley R E,Peterson D A,Gordon J I.Ecological and evolutionary forces shaping microbial diversity in the human intestine[J].Cell,2006,124(4):837-848.
[36]Freedberg D E,Lebwohl B,Abrams J A.The impact of proton pump inhibitors on the human gastrointestinal microbiome[J].Clin Lab Med,2014,34(4):771-785.
[2]郑玲利,蒋婷,李燕,等.2014-2016年成都25家医院质子泵抑制剂使用情况分析[J].现代药物与临床,2018,33(1):168-172.
[3]Lazarus B,Chen Y,Wilson F P,et al.Proton pump inhibitor use and the risk of chronic kidney disease[J].JAMA Intern Med,2016,176(2):238-246.
[4]Dipanda M,Pioro L,Buttard M,et al.Evaluation of the prescription of proton pump inhibitors in persons aged75years and older in a geriatric acute-care unit[J].Therapie,2017,72(6):669-675.
[5]张钰,罗璨.2014-2016年南京地区34家医院质子泵抑制剂的使用情况分析[J].现代药物与临床,2018,33(12):3354-3360.
[6]Wallerstedt S M,Fastbom J,Linke J,et al.Long-term use of proton pump inhibitors and prevalence of diseaseand drug-related reasons for gastroprotection-a crosssectional population-based study[J].Pharmacoepidemiol Drug Saf,2017,26(1):9-16.
[7]Lin S M,Yang S H,Liang C C,et al.Proton pump inhibitor use and the risk of osteoporosis and fracture in stroke patients:a population-based cohort study[J].Osteoporos Int,2018,29(1):153-162.
[8]Urbina Soto L1,Garcíaávila S1,Córdoba Alonso A I.Clostridium difficile associated diarrhoea:An increased problem[J].Med Clin(Barc),2016,147(12):543-546.
[9]Hafiz R A,Wong C,Paynter S,et al.The risk of community-acquired enteric infection in proton pump inhibitor therapy:systematic review and meta-analysis[J].Ann Pharmacother,2018,52(7):613-622.
[10]Krzych?J,?ój P,Nowak T et al.Short-term proton pump inhibitor treatment may cause hypomagnesaemia in critically ill patients-a pilot study[J].Acta Biochim Pol,2017,64(3):499-501.
[11]Dharmarajan T S,Kanagala M R,Murakonda P,et al.Do acid-lowering agents affect vitamin B12 status in older adults?[J].J Am Med Dir Assoc,2008,9(3):162-167.
[12]Haenisch B,von Holt K,Wiese B,et al.Risk of dementia in elderly patients with the use of proton pump inhibitors[J].Eur Arch Psychiatry Clin Neurosci,2015,265(5):419-428.
[13]Kuller L H.Do proton pump inhibitors increase the risk of dementia?[J].JAMA Neurol,2016,73(4):379-381.
[14]Akter S,Hassan M R,Shahriar M,et al.Cognitive impact after short-term exposure to different proton pump inhibitors:assessment using CANTAB software[J].Alzheimers Res Ther,2015,7:79.
[15]Gomm W,von Holt K,ThoméF,et al.Association of proton pump inhibitors with risk of dementia:a pharmacoepidemiological claims data analysis[J].JAMA Neurol,2016,73(4):410-416.
[16]Tai S Y,Chien C Y,Wu D C,et al.Risk of dementia from proton pump inhibitor use in Asian population:a nationwide cohort study in Taiwan[J].PLo S One,2017,12(2):e0171006.
[17]Moayyedi P,Lewis M A.Proton pump inhibitors and dementia:deciphering the data[J].Am J Gastroenterol,2017,112(12):1809-1811.
[18]Taipale H,Tolppanen A M,Tiihonen M,et al.No association between proton pump inhibitor use and risk of Alzheimer's disease[J].Am J Gastroenterol,2017,112(12):1802-1808.
[19]Hooshmand B,Solomon A,K?reholt I,et al.Homocysteine and holotranscobalamin and the risk of Alzheimer disease:a longitudinal study[J].Neurology,2010,75(16):1408-1414.
[20]Badiola N,Alcalde V,Pujol A,et al.The proton-pump inhibitor lansoprazole enhances amyloid beta production[J].PLo S One,2013,8(3):e58837.
[21]Maes M L,Fixen D R,Linnebur S A.Adverse effects of proton-pump inhibitor use in older adults:a review of the evidence[J].Ther Adv Drug Saf,2017,8(9):273-297.
[22]Fallahzadeh M K,Borhani Haghighi A,Namazi M R.Proton pump inhibitors:predisposers to Alzheimer disease?[J].J Clin Pharm Ther,2010,35(2):125-126.
[23]Majumdar A,Cruz D,Asamoah N,et al.Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils[J].Mol Biol Cell,2007,18(4):1490-1496.
[24]Namazi M R,Jowkar F.A succinct review of the general and immunological pharmacologic effects of proton pump inhibitors[J].J Clin Pharm Ther,2008,33(3):215-217.
[25]Spires-Jones T L,Meyer-Luehmann M,Osetek J D,et al.Impaired spine stability underlies plaque-related spine loss in an Alzheimer's disease mouse model[J].Am J Pathol,2007,171(4):1304-1311.
[26]Gong Y,Chang L,Viola K L,et al.Alzheimer's disease-affected brain:presence of oligomeric A beta ligands(ADDLs)suggests a molecular basis for reversible memory loss[J].Proc Natl Acad Sci U S A.2003,100(18):10417-10422.
[27]Haass C,Selkoe D J.Soluble protein oligomers in neurodegeneration:lessons from the Alzheimer's amyloid beta-peptide[J].Nat Rev Mol Cell Biol,2007,8(2):101-112.
[28]Gandy S.The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease[J].J Clin Invest,2005,115(5):1121-1129.
[29]Lam J R,Schneider J L,Zhao W,et al.Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency[J].JAMA,2013,310(22):2435-2442.
[30]Reynolds E.Vitamin B12,folic acid,and the nervous system[J].Lancet Neurol,2006,5(11):949-960.
[31]McCracken C,Hudson P,Ellis R,et al.Methylmalonic acid and cognitive function in the Medical Research Council Cognitive Function and Ageing Study[J].Am JClin Nutr,2006,84(6):1406-1411.
[32]Smith A D,Refsum H,Bottiglieri T,et al.Homocysteine and dementia:an international consensus statement[J].J Alzheimers Dis,2018,62(2):561-570.
[33]Christine C W,Auinger P,Joslin A,et al.Vitamin B12and homocysteine levels predict different outcomes in early Parkinson's disease[J].Mov Disord,2018,33(5):762-770.
[34]Banack S A,Caller T A,Stommel E W.The cyanobacteria derived toxin Beta-N-methylamino-L-alanine and amyotrophic lateral sclerosis[J].Toxins(Basel),2010,2(12):2837-2850.
[35]Ley R E,Peterson D A,Gordon J I.Ecological and evolutionary forces shaping microbial diversity in the human intestine[J].Cell,2006,124(4):837-848.
[36]Freedberg D E,Lebwohl B,Abrams J A.The impact of proton pump inhibitors on the human gastrointestinal microbiome[J].Clin Lab Med,2014,34(4):771-785.