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成都中医药大学 附属医院,成都 610072
Published:05 July 2023,
Published Online:17 November 2022,
Received:11 September 2022,
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王少锋,郝彦伟,李佳欣等.益气化痰类中药复方对阿尔茨海默病神经保护作用的研究进展[J].中国实验方剂学杂志,2023,29(13):222-229.
WANG Shaofeng,HAO Yanwei,LI Jiaxin,et al.Neuroprotective Effect of Chinese Medicinal Compounds Effective in Supplementing Qi and Resolving Phlegm on Alzheimer's Disease: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(13):222-229.
王少锋,郝彦伟,李佳欣等.益气化痰类中药复方对阿尔茨海默病神经保护作用的研究进展[J].中国实验方剂学杂志,2023,29(13):222-229. DOI: 10.13422/j.cnki.syfjx.20222106.
WANG Shaofeng,HAO Yanwei,LI Jiaxin,et al.Neuroprotective Effect of Chinese Medicinal Compounds Effective in Supplementing Qi and Resolving Phlegm on Alzheimer's Disease: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(13):222-229. DOI: 10.13422/j.cnki.syfjx.20222106.
阿尔茨海默病(AD)是一种老年人常见的慢性退行性神经性疾病,主要表现为认知、记忆和行为等方面的损害。当前该病病因和发病机制尚未完全明确,用于缓解疾病进展的相关药物研究仍处于临床试验中。中医认为老年人脏腑功能低下,正气亏虚,痰浊蒙窍是AD发生的核心病机,气虚痰阻贯穿AD的整个病理过程,治疗上强调益气化痰的重要作用。近年来,以开心散为代表的益气化痰类中药复方被广泛用于AD的临床和基础研究,发现其不仅可以改善AD的认知功能,还具有减少
β
淀粉样蛋白(A
β
)沉积、抑制tau蛋白过度磷酸化、改善神经递质活性、调节神经元突触可塑性、抗氧化应激损伤、抑制中枢炎性反应、抑制神经细胞凋亡等重要的神经保护作用。基于此,该文从益气化痰治疗AD的视角出发,对益气化痰治疗AD的理论基础及益气化痰类中药复方抗AD的作用机制研究进行了综述和分析,以期为中医药防治AD的临床应用提供理论支持和科学依据。
Alzheimer's disease (AD) is a common chronic degenerative neurological disease in the elderly and is mainly manifested by the impairment of cognition, memory, and behaviors. At present, the etiology and pathogenesis of this disease have not been fully unraveled, and the research on related drugs for alleviating the disease progression is still in clinical trials. Traditional Chinese medicine (TCM) believes that the elderly have reduced visceral function. Deficiency of vital Qi and turbid phlegm obscuring orifices are the core pathogenesis of AD. Qi deficiency and phlegm obstruction run through the whole pathological process of AD, and the important role of therapeutic principles of supplementing Qi and resolving phlegm is emphasized in treatment. In recent years, the Chinese medicinal compounds effective in supplementing Qi and resolving phlegm represented by Kaixin Powder have been widely used in the clinical and basic research of AD. As reported, in addition to the improvement of the cognitive function of AD, it can also reduce
β
amyloid (A
β
) deposition, inhibit tau hyperphosphorylation, improve neurotransmitter activity, regulate neuronal synaptic plasticity, resist oxidant stress injury, and inhibit the central inflammatory response and neuronal apoptosis. Therefore, this article reviewed and analyzed the theoretical basis of the treatment of AD by supplementing Qi and resolving phlegm and the mechanism of Chinese medicinal compounds effective in supplementing qi and resolving phlegm against AD to provide theoretical support and a scientific basis for the clinical application of TCM in the prevention and treatment of AD.
益气化痰法阿尔茨海默病神经保护中药复方
method of supplementing Qi and resolving phlegmAlzheimer's diseaseneuroprotectionChinese medicinal compound
SORIA LOPEZ J A,GONZÁLEZ H M,LÉGER G C.Alzheimer's disease[J].Handb Clin Neurol,2019,167:231-255.
SENGOKU R.Aging and Alzheimer's disease pathology[J].Neuropathology,2020,40(1):22-29.
陈庆华,张凤强,李立新,等.阿尔茨海默病发病机制和诊断技术研究进展[J].中华老年心脑血管病杂志,2018,20(1):108-110.
BREIJYEH Z,KARAMAN R.Comprehensive REVIEW on Alzheimer's disease: Causes and treatment[J].Molecules,2020,25(24):E5789.
李婉琳,宋勋,叶亮,等.阿尔茨海默病发病机制及药物治疗方法研究进展[J].中国临床神经科学,2021,29(5):581-589,596.
王洋,赵福红,宫铭海,等.蛋白质组学在阿尔茨海默病早期诊断及中医药防治中的研究进展[J].中国实验方剂学杂志,2021,27(16):227-236.
郭静,李斌,谢沛俊,等.基于泛素-蛋白酶体途径探讨远志散“益气化痰开窍”治疗阿尔茨海默病的科学内涵[J].世界科学技术—中医药现代化,2021,23(7):2334-2339.
聂志玲,周小莉.阿尔茨海默病的中医病因病机探析[J].时珍国医国药,2020,31(6):1443-1444.
张玉莲,张连城,李强,等.660例老年性痴呆患者中医证候学研究[J].中医杂志,2015,56(3):235-239.
第五永长,田金洲,时晶.从清代名医陈士铎治疗痴呆学术特色谈脾脑相关[J].四川中医,2011,29(2):43-44.
第五永长.老年性痴呆“髓空痰浊”病机及治法再识[J].中医杂志,2016,57(12):1075-1077.
温晓强,第五永长.阿尔茨海默病从脾胃论治的理论基础[J].四川中医,2017,35(12):23-25.
于蓓蓓,周春祥,张静远.诌议从后天之本论治阿尔茨海默病[J].世界科学技术—中医药现代化,2015,17(2):338-342.
崔雨婷,王亚琦,王培昌.阿尔茨海默病中β淀粉样蛋白的生成及清除的调节[J].中国生物化学与分子生物学报,2021,37(2):176-181.
YAMAZAKI Y,KANEKIYO T.Blood-brain barrier dysfunction and the pathogenesis of Alzheimer's disease[J].Int J Mol Sci,2017,18(9):E1965.
ROSAS-HERNANDEZ H,CUEVAS E,RAYMICK J B,et al.Impaired amyloid beta clearance and brain microvascular dysfunction are present in the Tg-SwDI mouse model of Alzheimer's disease[J].Neuroscience,2020,440:48-55.
CARRANO A,HOOZEMANS J J,VAN DER VIES S M,et al.Neuroinflammation and blood-brain barrier changes in capillary amyloid angiopathy[J].Neurodegener Dis,2012,10(1-4):329-331.
李斌,李佳欣,郝彦伟,等.远志散对阿尔茨海默病模型小鼠学习记忆能力及海马紧密连接蛋白表达的影响[J].中医杂志,2022,63(6):557-563.
NALIVAEVA N N,TURNER A J.Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy[J].Br J Pharmacol,2019,176(18):3447-3463.
ZOU L B,MOURI A,IWATA N,et al.Inhibition of neprilysin by infusion of thiorphan into the hippocampus causes an accumulation of amyloid Beta and impairment of learning and memory[J].J Pharmacol Exp Ther,2006,317(1):334-340.
IWATA N,MIZUKAMI H,SHIROTANI K,et al.Presynaptic localization of neprilysin contributes to efficient clearance of amyloid-beta peptide in mouse brain[J].J Neurosci,2004,24(4):991-998.
LIN C Y,PERCHE F,IKEGAMI M,et al.Messenger RNA-based therapeutics for brain diseases: An animal study for augmenting clearance of beta-amyloid by intracerebral administration of neprilysin mRNA loaded in polyplex nanomicelles[J].J Control Release,2016,235:268-275.
王丽娜,夏文,杨玲玲,等.开心散对Aβ25-35诱导损伤SH-N-K神经细胞的保护作用及机制[J].毒理学杂志,2007,21(1):22-26.
WANG N,JIA Y M,ZHANG B,et al.Neuroprotective mechanism of Kai Xin San: Upregulation of hippocampal insulin-degrading enzyme protein expression and acceleration of amyloid-beta degradation[J].Neural Regen Res,2017,12(4):654-659.
QUAN Q,WANG J,LI X,et al.Ginsenoside Rg1 decreases Aβ1-42 level by upregulating PPARγ and IDE expression in the hippocampus of a rat model of Alzheimer's disease[J].PLoS One,2013,8(3):e59155.
GU W J,LIU D,ZHANG M R,et al.Effect of ginsenoside Rb1 on insulin signal transduction pathway in hippocampal neurons of high-glucose-fed rats[J].Chin J Chin Mater Med,2014,39(6):1064-1068.
NASERI N N,WANG H,GUO J,et al.The complexity of tau in Alzheimer's disease[J].Neurosci Lett,2019,705:183-194.
TIWARI S,ATLURI V,KAUSHIK A,et al.Alzheimer's disease: Pathogenesis, diagnostics, and therapeutics[J].Int J Nanomedicine,2019,14:5541-5554.
YANG W,LIU Y,XU Q Q,et al.Sulforaphene ameliorates neuroinflammation and hyperphosphorylated Tau protein via regulating the PI3K/Akt/GSK-3β pathway in experimental models of Alzheimer's disease[J].Oxid Med Cell Longev,2020,2020:4754195.
LONG H Z,CHENG Y,ZHOU Z W,et al.PI3K/Akt signal pathway: A target of natural products in the prevention and treatment of Alzheimer's disease and Parkinson's disease[J].Front Pharmacol,2021,12:648636.
谢沛俊,郝彦伟,郭静,等.基于PI3K/AKT/GSK-3β通路探讨远志散调控阿尔兹海默病大鼠tau蛋白磷酸化的研究[J].中华中医药学刊,2020,38(11):167-170,后插22-22,后插28.
GUO S,WANG J,XU H,et al.Classic prescription, Kai-Xin-San, Ameliorates Alzheimer's disease as an effective multitarget treatment: From neurotransmitter to protein signaling pathway[J].Oxid Med Cell Longev,2019,2019:9096409.
GUO S,WANG J,WANG Y,et al.Study on the multitarget synergistic effects of Kai-Xin-San against Alzheimer's disease based on systems biology[J].Oxid Med Cell Longev,2019,2019:1707218.
李斌,谢沛俊,向劲松,等.远志散对阿尔茨海默病大鼠空间认知能力的影响及其机制研究[J].中药材,2020,43(9):2238-2243.
HARRIS L D,JASEM S,LICCHESI J.The ubiquitin system in Alzheimer's disease[J].Adv Exp Med Biol,2020,1233:195-221.
GADHAVE K,BOLSHETTE N,AHIRE A,et al.The ubiquitin proteasomal system: A potential target for the management of Alzheimer's disease[J].J Cell Mol Med,2016,20(7):1392-1407.
SCHMIDT M F,GAN Z Y,KOMANDER D,et al.Ubiquitin signalling in neurodegeneration: Mechanisms and therapeutic opportunities[J].Cell Death Differ,2021,28(2):570-590.
李佳欣,郝彦伟,王少锋,等.基于泛素-蛋白酶体系统探讨远志散改善快速老化小鼠学习记忆能力的作用机制[J].中华中医药杂志,2022,37(5):2929-2934.
FERREIRA-VIEIRA T H,GUIMARAES I M,SILVA F R,et al.Alzheimer's disease: Targeting the cholinergic system[J].Curr Neuropharmacol,2016,14(1):101-115.
王健,林水淼,周如倩,等.调心方治疗阿尔茨海默氏病的临床研究[J].北京中医药大学学报,2002,25(3):51-53.
刘学源,赵伟康,徐品初,等.调心方对杏仁核注射Aβ25-35诱导的阿尔茨海默病模型大鼠的影响[J].中草药,2004,35(1):50-53.
许玉珉,沈晓明,兰瑞,等.开心散对APP/PS1小鼠学习记忆能力和突触功能的机制[J].中国实验方剂学杂志,2021,27(20):15-22.
李牧函,张静,赵润清,等.6首开心散类方对阿尔兹海默病模型小鼠的药理作用及机制研究[J].中国中药杂志,2016,41(7):1269-1274.
李斌,孙中莉,陈冠儒,等.远志散对东莨菪碱致记忆获得性障碍模型小鼠行为学和脑内AchE活性的影响[J].广州中医药大学学报,2017,34(5):733-736.
杨丽霞,赵婧,王善,等.党参远志散微乳对阿尔茨海默病模型小鼠学习记忆障碍的改善作用[J].中草药,2020,51(5):1257-1263.
杨丽霞,赵晶晶,王颖莉.党参远志散微乳提取液对AD小鼠海马亚区AchE、ChAT蛋白表达的影响[J].中华中医药学刊,2022,40(4):223-226.
王可,董林,张曦,等.多巴胺与神经退行性疾病研究进展[J].生命的化学,2014,34(2):184-192.
AMBRÉE O,RICHTER H,SACHSER N,et al.Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer's disease[J].Neurobiol Aging,2009,30(8):1192-1204.
GUTIÉRREZ I L,DELLO RUSSO C,NOVELLINO F,et al.Noradrenaline in Alzheimer's disease: A new potential therapeutic target[J].Int J Mol Sci,2022,23(11)
CHAKRABORTY S,LENNON J C,MALKARAM S A,et al.Serotonergic system, cognition, and BPSD in Alzheimer's disease[J].Neurosci Lett,2019,704:36-44.
刘帅,彭良玉,刘甜甜,等.中枢5-HT系统和阿尔茨海默病的相关性[J].中国老年学杂志,2022,42(6):1517-1524.
师冉,宗鑫,滕佳林,等.开心散对SAMP8小鼠神经递质的影响[J].中国老年学杂志,2017,37(21):5249-5251.
陈书仪,孙洁,郭爱,等.突触可塑性与阿尔茨海默病[J].生命的化学,2017,37(4):607-611.
SKAPER S D,FACCI L,ZUSSO M,et al.Synaptic plasticity, dementia and Alzheimer disease[J].CNS Neurol Disord Drug Targets,2017,16(3):220-233.
COLUCCI-D'AMATO L,SPERANZA L,VOLPICELLI F.Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer[J].Int J Mol Sci,2020,21(20):7777.
王登坤,第五永长,苟于瑞,等.洗心汤对阿尔茨海默病模型大鼠海马BDNF、TrKB蛋白表达及肠道菌群多样性的影响[J].中医杂志,2021,62(15):1362-1369.
王晓雯,邓海燕,王健,等.环磷酸腺苷效应元件结合蛋白/脑源性神经营养因子信号通路在调心方改善APP/PS1小鼠学习记忆中的作用[J].中国康复理论与实践,2018,24(1):11-16.
王晓雯,钱红,沈春娟,等.基于αCaMKⅡ-CREB-BDNF信号通路研究调心方对APP/PS1双转基因AD小鼠学习记忆和突触可塑性的影响[J].康复学报,2020,30(4):299-306.
王晓雯,邓海燕,王健,等.调心方对APP/PS1双转基因AD小鼠空间学习记忆能力和海马突触传递长时程增强的影响[J].中国中医药信息杂志,2017,24(10):40-43.
GOETZL E J,KAPOGIANNIS D,SCHWARTZ J B,et al.Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease[J].FASEB J,2016,30(12):4141-4148.
CALSOLARO V,EDISON P.Neuroinflammation in Alzheimer's disease: Current evidence and future directions[J].Alzheimers Dement,2016,12(6):719-732.
米彩云,王虎平.阿尔茨海默病免疫炎症机制的研究进展[J].中国老年学杂志,2022,42(11):2837-2841.
吴艺舸,王泽乾,殷丽君,等.小胶质细胞吞噬在阿尔茨海默病不同阶段的作用及其机制[J].中国病理生理杂志,2022,38(4):735-742.
孙泉,金国琴,赵伟康,等.调心方对氧化损伤型类AD大鼠脑组织淀粉样蛋白(APP) mRNA表达的影响[J].中药药理与临床,2003,19(2):28-31.
师冉,季旭明,董丽雪,等.开心散对快速老化痴呆小鼠SAMP8炎症因子及β-APP影响随机平行对照研究[J].实用中医内科杂志,2013,27(13):101-104.
LUO Y,LI D,LIAO Y,et al.Systems pharmacology approach to investigate the mechanism of Kai-Xin-San in Alzheimer's disease[J].Front Pharmacol,2020,11:381.
刘志涛,王钦文,李广宇,等.有氧运动对阿尔茨海默病认知功能的影响及其机制[J].生物化学与生物物理进展,2020,47(9):923-934.
周玲玲,钱康,杨鹏,等.阿尔茨海默病的线粒体氧化应激及靶向递送系统研究进展[J].药学学报,2022,57(6):1630-1640.
郭静,李斌,王智超,等.远志散对D-半乳糖致衰老小鼠学习记忆及氧化应激水平的影响[J].中华中医药学刊,2019,37(9):2144-2147,2314.
杨丽霞,赵婧,郭亚菲,等.生物相容性党参远志散微乳对AD模型小鼠学习记忆的影响[J].中华中医药杂志,2020,35(4):1732-1735.
MUTISYA E M,BOWLING A C,BEAL M F.Cortical cytochrome oxidase activity is reduced in Alzheimer's disease[J].J Neurochem,1994,63(6):2179-2184.
康湘萍,金国琴,赵伟康,等.调心方有效部位TX0201对Aβ25-35所致类“AD”大鼠氧化损伤及能量代谢的影响[J].中药药理与临床,2005,21(2):23-26.
熊春伟,张宪亮.运动调控PI3K/Akt信号通路改善阿尔茨海默病的研究进展[J].中国康复医学杂志,2021,36(10):1322-1326.
SHARMA V K,SINGH T G,SINGH S,et al.Apoptotic pathways and Alzheimer's disease: Probing therapeutic potential[J].Neurochem Res,2021,46(12):3103-3122.
苟于瑞,第五永长,王登坤,等.洗心汤组分配伍对D-半乳糖联合Aβ25-35致AD模型大鼠学习记忆能力的影响及主要机制探讨[J].时珍国医国药,2021,32(11):2585-2589.
DU H,SHIDU YAN S.Unlocking the door to neuronal woes in Alzheimer's disease: Aβ and mitochondrial permeability transition pore[J].Pharmaceuticals (Basel),2010,3(6):1936-1948.
JOHNSON J,MERCADO-AYON E,MERCADO-AYON Y,et al.Mitochondrial dysfunction in the development and progression of neurodegenerative diseases[J].Arch Biochem Biophys,2021,702:108698.
邵怡然,第五永长,曾健,等.洗心汤对Aβ1-42诱导的海马神经元线粒体功能的影响[J].辽宁中医杂志,2018,45(6):1281-1284,后插4.
师冉,季旭明,滕佳林,等.开心散改善SAMP8小鼠mtDNA表达及对凋亡相关基因的影响[J].山东中医药大学学报,2017,41(4):368-371.
张赫,郑焱.β淀粉样蛋白级联假说相关的阿尔茨海默病发病机制及防治策略研究进展[J].中国医学科学院学报,2019,41(5):702-708.
吴东南,刘玲,明淑萍,等.基于“Aβ异常沉积”浅析中医“从痰论治”阿尔茨海默病[J].中华中医药杂志,2019,34(10):4699-4702.
余梦瑶,许晓燕,江南,等.阿尔茨海默症痰湿蕴结与β-淀粉样肽聚集及自噬相关性探讨[J].中华中医药杂志,2016,31(9):3632-3635.
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