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中华针灸电子杂志 ›› 2025, Vol. 14 ›› Issue (01) : 28 -33. doi: 10.3877/cma.j.issn.2095-3240.2025.01.006

综述

基于大脑类淋巴系统清除机制探讨针刺治疗阿尔茨海默病的研究进展
袁紫嫣1,2, 姚春玲1,2, 石江伟1,2,   
  1. 1. 300381 天津中医药大学第一附属医院针灸部
    2. 300381 天津,国家中医针灸临床医学研究中心
  • 收稿日期:2024-03-20 出版日期:2025-02-15
  • 通信作者: 石江伟
  • 基金资助:
    国家自然科学基金(82374560)天津市中医药重点领域科研项目(2023011)

Research progress on acupuncture treatment for Alzheimer′s disease based on the mechanism of brain-like lymphatic clearance mechanism

Ziyan Yuan1,2, Chunling Yao1,2, Jiangwei Shi1,2,   

  1. 1. Department of Acupuncture,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300381,China
    2. National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin 300381,China
  • Received:2024-03-20 Published:2025-02-15
  • Corresponding author: Jiangwei Shi
引用本文:

袁紫嫣, 姚春玲, 石江伟. 基于大脑类淋巴系统清除机制探讨针刺治疗阿尔茨海默病的研究进展[J/OL]. 中华针灸电子杂志, 2025, 14(01): 28-33.

Ziyan Yuan, Chunling Yao, Jiangwei Shi. Research progress on acupuncture treatment for Alzheimer′s disease based on the mechanism of brain-like lymphatic clearance mechanism[J/OL]. Chinese Journal of Acupuncture and Moxibustion(Electronic Edition), 2025, 14(01): 28-33.

阿尔茨海默病(AD)的病因及发病机制复杂,目前尚不明确,现代医学研究认为AD 的发病可能与衰老、遗传、自身免疫、环境等因素导致的脑内微环境改变及脑内代谢废物清除异常有关。近年来的研究发现类淋巴系统解释了中枢神经系统的免疫途径,也成为改善脑内微环境及认知障碍的新靶点。 综述类淋巴系统清除机制及其可能的影响因素,结合中医经络穴位探讨针刺对类淋巴系统及脑内代谢的作用机制,为今后调控类淋巴系统治疗AD 提供新的思路与方法。

The etiology and pathogenesis of Alzheimer′s disease are complex and still unclear,and modern medical research suggests that the onset of Alzheimer′s disease may be related to change in the cerebral microenvironment and abnormal clearance of metametabolic waste caused by aging,gheredity,autoimmunity,and environmental factors.Recent studies have found that the lymphoid system explains the immune pathways in the central nervous system and has become a new target for improving the brain microenvironment and cognitive disorders.This article reviews the mechanism of lymphoid system clearance and its possible influencing factors,and discusses the mechanism of acupuncture on lymphoid system and brain metabolism in combination with the meridian points of traditional Chinese medicine,so as to provide new ideas and methods for future modulation of lymphoid system in the treatment of Alzheimer′s disease.

1
GBD 2019 Dementia Forecasting Collaborators.Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019[J].Lancet Public Health,2022,7(2): e105-e125.
2
徐俊.阿尔茨海默病的ATN 诊断标准重塑血管性认知障碍诊治[J].中国卒中杂志,2019,14(2): 97-99.
3
Scheltens P,De Strooper B,Kivipelto M,et al.Alzheimer′s disease[J].Lancet,2021,397(10284): 1577-1590.
4
Iliff JJ,Wang M,Liao Y,et al.A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes,including amyloid β[J].Sci Transl Med,2012,4(147): 147ra111.
5
Aukland K,Reed RK.Interstitial-lymphatic mechanisms in the control of extracellular fluid volume[J].Physiol Rev,1993,73(1):1-78.
6
Plog BA,Nedergaard M.The glymphatic system in central nervous system health and disease: past,present,and future[J].Annu Rev Pathol,2018,13:379-394.
7
Abbott NJ.Evidence for bulk flow of brain interstitial fluid:significance for physiology and pathology[J].Neurochem Int,2004,45(4): 545-552.
8
Sun BL,Wang LH,Yang T,et al.Lymphatic drainage system of the brain: a novel target for intervention of neurological diseases[J].Prog Neurobiol,2018,163-164: 118-143.
9
Lohela TJ,Lilius TO,Nedergaard M.The glymphatic system:implications for drugs for central nervous system diseases[J].Nat Rev Drug Discov,2022,21(10): 763-779.
10
Preston GM,Carroll TP,Guggino WB,et al.Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein[J].Science,1992,256(5055): 385-387.
11
Jung JS,Bhat RV,Preston GM,et al.Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance[J].Proc Natl Acad Sci USA,1994,91(26): 13052-13056.
12
Nielsen S,Nagelhus EA,Amiry-Moghaddam M,et al.Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain [ J].J Neurosci,1997,17(1): 171-180.
13
Papadopoulos MC,Verkman AS.Aquaporin-4 and brain edema[J].Pediatr Nephrol,2007,22(6): 778-784.
14
Nedergaard M.Neuroscience.Garbage truck of the brain [ J].Science,2013,340(6140): 1529-1530.
15
Nagelhus EA,Ottersen OP.Physiological roles of aquaporin-4 in brain[J].Physiol Rev,2013,93(4): 1543-1562.
16
Xu Z,Xiao N,Chen Y,et al.Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits[J].Mol Neurodegener,2015,10: 58.
17
Munk AS,Wang W,Bèchet NB,et al.PPDGF-B is required for development of the glymphatic system[J].Cell Rep,2019,26(11): 2955-2969.e3.
18
Da Mesquita S,Fu Z,Kipnis J.The meningeal lymphatic system: a new player in neurophysiology [J].Neuron,2018,100 (2):375-388.
19
Louveau A,Plog BA,Antila S,et al.Understanding the functions and relationships of the glymphatic system and meningeal lymphatics[J].J Clin Invest,2017,127(9): 3210-3219.
20
Iliff JJ,Wang M,Zeppenfeld DM,et al.Cerebral arterial pulsation drives paravascular CSF - interstitial fluid exchange in the murine brain[J].J Neurosci,2013,33(46): 18190-18199.
21
Dreha-Kulaczewski S,Joseph AA,Merboldt KD,et al.Inspiration is the major regulator of human CSF flow[J].J Neurosci,2015,35(6): 2485-2491.
22
Hablitz LM,Plá V,Giannetto M,et al.Circadian control of brain glymphatic and lymphatic fluid flow[J].Nat Commun,2020,11(1): 4411.
23
Nilsson C,Ståhlberg F,Thomsen C,et al.Circadian variation in human cerebrospinal fluid production measured by magnetic resonance imaging[J].Am J Physiol,1992,262 (1 Pt 2):R20-R24.
24
Hablitz LM,Vinitsky HS,Sun Q,et al.Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia[J].Sci Adv,2019,5(2): eaav5447.
25
Xie L,Kang H,Xu Q,et al.Sleep drives metabolite clearance from the adult brain[J].Science,2013,342(6156): 373-377.
26
Rasmussen MK,Mestre H,Nedergaard M.The glymphatic pathway in neurological disorders[J].Lancet Neurol,2018,17(11):1016-1024.
27
Jiang-Xie LF,Drieu A,BhasIIn K,et al.Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance[J].Nature,2024,627(8002): 157-164.
28
Berezuk C,Ramirez J,Gao F,et al.Virchow-robin spaces:correlations with polysomnography-derived sleep parameters [J].Sleep 2015,38(6): 853-858.
29
Wardlaw JM,Benveniste H,Nedergaard M,et al.Perivascular spaces in the brain: anatomy,physiology and pathology[J].Nat Rev Neurol,2020,16(3): 137-153.
30
Lananna BV,Nadarajah CJ,Izumo M,et al.Cell-autonomous regulation of astrocyte activation by the circadian clock protein BMAL1[J].Cell Rep,2018,25(1): 1-9.e5.
31
Myung J,Schmal C,Hong S,et al.The choroid plexus is an important circadian clock component[J].Nat Commun,2018,9(1):1062.
32
Brancaccio M,Patton AP,Chesham JE,et al.Astrocytes control circadian timekeeping in the suprachiasmatic nucleus via glutamatergic signaling[J].Neuron,2017,93(6):1420-1435.e5.
33
Kress BT,Iliff JJ,Xia M,et al.Impairment of paravascular clearance pathways in the aging brain[J].Ann Neurol,2014,76(6): 845-861.
34
Ahn JH,Cho H,Kim JH,et al.Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid [ J].Nature,2019,572(7767): 62-66.
35
Balbi M,Ghosh M,Longden TA,et al.Dysfunction of mouse cerebral arteries during early aging[J].J Cereb Blood Flow Metab,2015,35(9): 1445-1453.
36
Knopman DS,Jack CR Jr,Wiste HJ,et al.Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia[J].Neurology,2016,87(7): 691-698.
37
Ma Q,Ineichen BV,Detmar M,et al.Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice[J].Nat Commun,2017,8(1):1434.
38
Trumbore CN.Shear-induced amyloid formation in the brain: I.potential vascular and parenchymal processes[J].J Alzheimers Dis,2016,54(2): 457-470.
39
Hawkes CA,Gatherer M,Sharp MM,et al.Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid-β from the mouse brain[J].Aging Cell,2013,12(2): 224-236.
40
Lim YY,Laws SM,Villemagne VL,et al.Aβ-related memory decline in APOE ε4 noncarriers: Implications for Alzheimer disease[J].Neurology,2016,86(17): 1635-1642.
41
Biundo F,Ishiwari K,Del Prete D,et al.Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like danish dementia: effects on learning and memory[J].Neurobiol Learn Mem,2015,126: 18-30.
42
Ringman JM,Sachs MC,Zhou Y,et al.Clinical predictors of severe cerebral amyloid angiopathy and influence of APOE genotype in persons with pathologically verified Alzheimer disease[J].JAMA Neurol,2014,71(7): 878-883.
43
Louveau A,Smirnov I,Keyes TJ,et al.Structural and functional features of central nervous system lymphatic vessels[J].Nature,2015,523(7560): 337-341.
44
Engelhardt B,Vajkoczy P,Weller RO.The movers and shapers in immune privilege of the CNS[J].Nat Immunol,2017,18(2):123-131.
45
Filiano AJ,Gadani SP,Kipnis J.How and why do T cells and their derived cytokines affect the injured and healthy brain? [J].Nat Rev Neurosci,2017,18(6): 375-384.
46
Gupta A,Iadecola C.Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer′s disease[J].Front Aging Neurosci,2015,7: 115.
47
Jiang Q ,Zhang L,Ding G ,et al.Impairment of the glymphatic system after diabetes[J].J Cereb Blood Flow Metab,2017,37(4):1326-1337.
48
Wang M,Ding F,Deng S,et al.Focal solute trapping and global glymphatic pathway impairment in a murine model of multiple microinfarcts[J].J Neurosci,2017,37(11): 2870-2877.
49
Iliff JJ,Chen MJ,Plog BA,et al.Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury[J].J Neurosci,2014,34(49): 16180-16193.
50
Gaberel T,Gakuba C,Goulay R,et al.Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: a new target for fibrinolysis? [J].Stroke,2014,45(10): 3092-3096.
51
樊小农,刘健,李谈,等.不同针刺法对P15 在SAMP8 不同脑区星型胶质细胞表达的影响[J].天津中医药,2007,24(6):503-506.
52
周雅然,张雪竹,沈鹏.针刺调控NLRC5 抑制NF-κB 通路减轻SAMP8 小鼠脑内神经炎症反应的研究[J].天津中医药,2021,38(1): 71-76.
53
曹育,安玉兰,张卓铭,等.针刺对阿尔茨海默症小鼠海马CA1 区树突结构及认知功能影响的研究[J].中国比较医学杂志,2021,31(10): 9-15.
54
薛卫国,张忠,白丽敏,等.电针对β-淀粉样前体蛋白转基因小鼠行为学及其淀粉样前体蛋白、β 淀粉样蛋白及胆碱乙酰转移酶水平的影响[J].针刺研究,2009,34(3): 152-158.
55
王媛媛,冯兆才,路岩莉.头部经络与癫痫的关系研究进展[J/OL].中华针灸电子杂志,2022,11(2): 55-57.
56
石江伟,庄朋伟.中医药调整脑内微环境改善阿尔兹海默病引发认知损伤作用效果及生物学机制研究进展[J].天津中医药,2020,37(4): 475-480.
57
Liang PZ,Li L,Zhang YN,et al.Electroacupuncture improves clearance of amyloid-β through the glymphatic system in the SAMP8 mouse model of Alzheimer′s disease[J].Neural Plast,2021,2021: 9960304.
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