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浙江大学学报(医学版)  2022, Vol. 51 Issue (1): 108-114    DOI: 10.3724/zdxbyxb-2021-0111
综述     
慢性牙周炎与帕金森病相关性的研究进展
边梦瑶,陈莉丽,雷利红()
浙江大学医学院附属第二医院牙周病专科, 浙江 杭州 310009
Research progress on the relationship between chronic periodontitis and Parkinson’s disease
BIAN Mengyao,CHEN Lili,LEI Lihong()
Department of Periodontology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
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摘要:

慢性牙周炎属于慢性感染性疾病,与多种全身疾病存在双向关系。帕金森病是一种常见的神经退行性变性疾病,炎症反应在其进展中起到一定作用。近年来,大量研究提示慢性牙周炎与帕金森病等神经退行性变性疾病之间存在潜在联系,帕金森病患者牙周状况较差,其口腔菌群组成与健康人群存在差异;与此同时,慢性牙周炎患者罹患帕金森病的风险更高,定期牙周治疗可能在一定程度上降低该风险。慢性牙周炎与帕金森病的相互作用机制尚未明确,部分研究认为帕金森病患者可能由于运动及非运动症状,无法有效维护口腔卫生,增加牙周炎患病风险;小胶质细胞介导的神经炎症则可能是慢性牙周炎影响帕金森病的关键,牙周致病菌及炎症介质或可通过多种途径进入大脑并激活小胶质细胞,最终影响帕金森病的发生发展。本文就慢性牙周炎与帕金森病相关性及可能的交互作用机制的最新研究进展作一综述,以期为进一步探讨两者相互影响的研究提供思路。

关键词: 慢性牙周炎帕金森病神经炎症小胶质细胞牙周致病菌综述    
Abstract:

Chronic periodontitis is an infectious disease, which has a reciprocal relationship with a variety of systemic disorders. Parkinson’s disease is a prevalent neurodegenerative disease in which inflammation plays an important role for its progression. A vast number of studies suggest that there is a potential connection between chronic periodontitis and neurodegenerative diseases such as Parkinson’s disease. Individuals with Parkinson’s disease usually have poor periodontal health, and their oral flora composition differs from that of healthy people; at the same time, patients with chronic periodontitis have a higher risk of Parkinson’s disease, which can be reduced with regular periodontal treatment. In fact, the mechanism of interaction between chronic periodontitis and Parkinson’s disease is not clear. According to several studies, the clinical symptoms of Parkinson’s disease prevent patients to maintain oral hygiene effectively, increasing the risk of periodontitis. Neuroinflammation mediated by microglia may be the key to the influence of chronic periodontitis on Parkinson’s disease. Periodontal pathogens and inflammatory mediators may enter the brain and activate microglia in various ways, and ultimately leading to occurrence and development of Parkinson’s disease. This article reviews the recent research progress on the association between chronic periodontitis and Parkinson’s disease, and its potential mechanism to provide information for further research.

Key words: Chronic periodontitis    Parkinson’s disease    Neuroinflammation    Microglia    Periodontal bacteria    Review
收稿日期: 2021-10-24 出版日期: 2022-05-17
CLC:  R781.4  
通讯作者: 雷利红     E-mail: kqllh@zju.edu.cn
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边梦瑶,陈莉丽,雷利红. 慢性牙周炎与帕金森病相关性的研究进展[J]. 浙江大学学报(医学版), 2022, 51(1): 108-114.

BIAN Mengyao,CHEN Lili,LEI Lihong. Research progress on the relationship between chronic periodontitis and Parkinson’s disease. J Zhejiang Univ (Med Sci), 2022, 51(1): 108-114.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0111        https://www.zjujournals.com/med/CN/Y2022/V51/I1/108

1 王 兴. 第四次全国口腔健康流行病学调查报告[M]. 北京: 人民卫生出版社, 2018: 106-113
2 GENCOR J, SANZM. Clinical and public health implications of periodontal and systemic diseases: an overview[J]Periodontol 2000, 2020, 83( 1): 7-13.
doi: 10.1111/prd.12344
3 刘疏影, 陈 彪. 帕金森病流行现状[J]. 中国现代神经疾病杂志, 2016, 16(2): 98-101
LIU Shuying, CHEN Biao. Epidemiology of Parkinson’s disease[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2016, 16(2): 98-101. (in Chinese)
4 DORSEYE R, CONSTANTINESCUR, THOMPSONJ P, et al.Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030[J]Neurology, 2007, 68( 5): 384-386.
doi: 10.1212/01.wnl.0000247740.47667.03
5 KALIAL V, LANGA E. Parkinson’s disease[J]Lancet, 2015, 386( 9996): 896-912.
doi: 10.1016/S0140-6736(14)61393-3
6 DICKSOND W, BRAAKH, DUDAJ E, et al.Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria[J]Lancet Neurol, 2009, 8( 12): 1150-1157.
doi: 10.1016/s1474-4422(09)70238-8
7 JOHNSONM E, STECHERB, LABRIEV, et al.Triggers, facilitators, and aggravators: redefining parkinson’s disease pathogenesis[J]Trends Neuroscis, 2019, 42( 1): 4-13.
doi: 10.1016/j.tins.2018.09.007
8 BURBULLAL F, SONGP, MAZZULLIJ R, et al.Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease[J]Science, 2017, 357( 6357): 1255-1261.
doi: 10.1126/science.aam9080
9 PUSPITAL, CHUNGS Y, SHIMJ W. Oxidative stress and cellular pathologies in Parkinson’s disease[J]Mol Brain, 2017, 10( 1): 53.
doi: 10.1186/s13041-017-0340-9
10 YANJ, FUQ, CHENGL, et al.Inflammatory response in Parkinson’s disease (Review)[J]Mol Med Rep, 2014, 10( 5): 2223-2233.
doi: 10.3892/mmr.2014.2563
11 李 琳, 王 丹, 赵曼竹, 等. 慢性牙周炎与神经退行性疾病相关性的研究进展[J]. 国际口腔医学杂志, 2017, 44(5): 514-518
LI Lin, WANG Dan, ZHAO Manzhu, et al. Research progress on the correlation between chronic periodontitis and neurodegenerative diseases[J]. Internation Journal of Stomatology, 2017, 44(5): 514-518. (in Chinese)
12 HASHIOKAS, INOUEK, MIYAOKAT, et al.The possible causal link of periodontitis to neuropsychiatric disorders: more than psychosocial mechanisms[J]Int J Mol Sci, 2019, 20( 15): 3723.
doi: 10.3390/ijms20153723
13 钱雪申, 葛 颂. 慢性牙周炎与阿尔茨海默病关系的研究现状[J]. 中华口腔医学杂志, 2018, 53(4): 275-279
QIAN Xueshen, GE Song.The state of the art research findings on the relationship between chronic periodontitis and Alzheimer’s disease: a review[J]. Chinese Journal of Stomatology, 2018, 53(4): 275-279. (in Chinese)
14 SCHWARZJ, HEIMHILGERE, STORCHA. Increased periodontal pathology in Parkinson’s disease[J]J Neurol, 2006, 253( 5): 608-611.
doi: 10.1007/s00415-006-0068-4
15 EINARSDÓTTIRE R, GUNNSTEINSDÓTTIRH, HALLSDÓTTIRM H, et al.Dental health of patients with Parkinson’s disease in Iceland[J]Spec Care Dent, 2009, 29( 3): 123-127.
doi: 10.1111/j.1754-4505.2009.00075.x
16 HANAOKAA, KASHIHARAK. Increased frequencies of caries, periodontal disease and tooth loss in patients with Parkinson’s disease[J]J Clin Neurosci, 2009, 16( 10): 1279-1282.
doi: 10.1016/j.jocn.2008.12.027
17 MÜLLERT, PALLUCHR, ACKOWSKIJ J. Caries and periodontal disease in patients with Parkinson’s disease[J]Spec Care Dent, 2011, 31( 5): 178-181.
doi: 10.1111/j.1754-4505.2011.00205.x
18 PRADEEPA R, SINGHS P, MARTANDES S, et al.Clinical evaluation of the periodontal health condition and oral health awareness in Parkinson’s disease patients[J]Gerodontology, 2015, 32( 2): 100-106.
doi: 10.1111/ger.12055
19 BAKKEM, LARSENS L, LAUTRUPC, et al.Orofacial function and oral health in patients with Parkinson’s disease[J]Eur J Oral Sci, 2011, 119( 1): 27-32.
doi: 10.1111/j.1600-0722.2010.00802.x
20 VAN STIPHOUTM A E, MARINUSJ, VAN HILTENJ J, et al.Oral health of parkinson’s disease patients: a case-control study[J]Parkinsons Dis, 2018, 1-8.
doi: 10.1155/2018/9315285
21 LYRAP, MACHADOV, PROENÇAL, et al.Parkinson’s disease, periodontitis and patient-related outcomes: a cross-sectional study[J]Medicina, 2020, 56( 8): 383.
doi: 10.3390/medicina56080383
22 PATINIR. Oral microbiota: discovering and facing the new associations with systemic diseases[J]Pathogens, 2020, 9( 4): 313.
doi: 10.3390/pathogens9040313
23 PEREIRAP A B, AHOV T E, PAULINL, et al.Oral and nasal microbiota in Parkinson’s disease[J]Parkinsonism Relat Disord, 2017, 61-67.
doi: 10.1016/j.parkreldis.2017.02.026
24 ROZASN S, TRIBBLEG D, JETERC B. Oral factors that impact the oral microbiota in parkinson’s disease[J]Microorganisms, 2021, 9( 8): 1616.
doi: 10.3390/microorganisms9081616
25 FLEURYV, ZEKERIDOUA, LAZAREVICV, et al.Oral dysbiosis and inflammation in Parkinson’s disease[J]J Parkinson Dis, 2021, 11( 2): 619-631.
doi: 10.3233/JPD-202459
26 MIHAILAD, DONEGANJ, BARNSS, et al.The oral microbiome of early stage Parkinson’s disease and its relationship with functional measures of motor and non-motor function[J/OL]PLoS One, 2019, 14( 6): e0218252.
doi: 10.1371/journal.pone.0218252
27 KAURT, UPPOORA, NAIKD. Parkinson’s disease and periodontitis——the missing link? A review[J]Gerodontology, 2016, 33( 4): 434-438.
doi: 10.1111/ger.12188
28 SHENC C, TSAIS J, PERNGC L, et al.Risk of Parkinson disease after depression: a nationwide population-based study[J]Neurology, 2013, 81( 17): 1538-1544.
doi: 10.1212/WNL.0b013e3182a956ad
29 SABBAHW, GOMAAN, GIREESHA. Stress, allostatic load, and periodontal diseases[J]Periodontol 2000, 2018, 78( 1): 154-161.
doi: 10.1111/prd.12238
30 LIUT C, SHEUJ J, LINH C, et al.Increased risk of parkinsonism following chronic periodontitis: a retrospective cohort study[J]Mov Disord, 2013, 28( 9): 1307-1308.
doi: 10.1002/mds.25359
31 CHENC K, WUY T, CHANGY C. Periodontal inflammatory disease is associated with the risk of Parkinson’s disease: a population-based retrospective matched-cohort study[J/OL]PeerJ, 2017, e3647.
doi: 10.7717/peerj.3647
32 JEONGE, PARKJ B, PARKY G. Evaluation of the association between periodontitis and risk of Parkinson’s disease: a nationwide retrospective cohort study[J]Sci Rep, 2021, 11( 1): 16594.
doi: 10.1038/s41598-021-96147-4
33 WOOH G, CHANGY, LEEJ S, et al.Association of tooth loss with new-onset Parkinson’s disease: a nationwide population-based cohort study[J]Parkinsons Dis, 2020, 4760512.
doi: 10.1155/2020/4760512
34 CHENC K, HUANGJ Y, WUY T, et al.Dental scaling decreases the risk of Parkinson’s disease: a nationwide population-based nested case-control study[J]Int J Environ Res Public Health, 2018, 15( 8): 1587.
doi: 10.3390/ijerph15081587
35 LEDWONB, MISKIEWICZA, GRABOWSKAE, et al.The relationship between periodontal disease and motor impairment in the course of Parkinson’s disease[J]Postepy Hig Med Dosw, 2020, 340-347.
doi: 10.5604/01.3001.0014.3516
36 FROSTJ L, SCHAFERD P. Microglia: architects of the developing nervous system[J]Trends Cell Biol, 2016, 26( 8): 587-597.
doi: 10.1016/j.tcb.2016.02.006
37 GERHARDA, PAVESEN, HOTTONG, et al.In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease[J]NeuroBiol Dis, 2006, 21( 2): 404-412.
doi: 10.1016/j.nbd.2005.08.002
38 申 杰, 徐桂华. 血脑屏障与中枢神经系统疾病的相关性研究进展[J]. 中华神经医学杂志, 2020, 19(9): 961-965
SHEN Jie, XU Guihua. Recent advance in relation between blood-brain barrier and central nervous system diseases[J]. Chinese Journal of Neuromedicine, 2020, 19(9): 961-965. (in Chinese)
39 GRAYM T, WOULFEJ M. Striatal blood-brain barrier permeability in Parkinson’s disease[J]J Cereb Blood Flow Metab, 2015, 35( 5): 747-750.
doi: 10.1038/jcbfm.2015.32
40 DICKSTEINJ B, MOLDOFSKYH, HAYJ B. Brain-blood permeability: TNF-α promotes escape of protein tracer from CSF to blood[J]Am J Physiol-Regulatory Integrative Comp Physiol, 2000, 279( 1): R148-R151.
doi: 10.1152/ajpregu.2000.279.1.R148
41 NAVARATHNAD H M L P, MUNASINGHEJ, LIZAKM J, et al.MRI confirms loss of blood-brain barrier integrity in a mouse model of disseminated candidiasis[J]NMR Biomed, 2013, 26( 9): 1125-1134.
doi: 10.1002/nbm.2926
42 FRYM, FERGUSONA V. The sensory circumventricular organs: brain targets for circulating signals controlling ingestive behavior[J]Physiol Behav, 2007, 91( 4): 413-423.
doi: 10.1016/j.physbeh.2007.04.003
43 WARDLAWJ M, BENVENISTEH, NEDERGAARDM, et al.Perivascular spaces in the brain: anatomy, physiology and pathology[J]Nat Rev Neurol, 2020, 16( 3): 137-153.
doi: 10.1038/s41582-020-0312-z
44 FREIREM, NELSONK E, EDLUNDA. The oral host——microbial interactome: an ecological chronometer of health?[J]Trends Microbiol, 2021, 29( 6): 551-561.
doi: 10.1016/j.tim.2020.11.004
45 XUEL, ZOUX, YANGX Q, et al.Chronic periodontitis induces microbiota-gut-brain axis disorders and cognitive impairment in mice[J]Exp Neurol, 2020, 113176.
doi: 10.1016/j.expneurol.2020.113176
46 LANZAE, MAGAN-FERNANDEZA, BERMEJOB, et al.Complementary clinical effects of red complex bacteria on generalized periodontitis in a caucasian population[J]Oral Dis, 2016, 22( 5): 430-437.
doi: 10.1111/odi.12471
47 DOMINYS S, LYNCHC, ERMINIF, et al.Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors[J/OL]Sci Adv, 2019, 5( 1): eaau3333.
doi: 10.1126/sciadv.aau3333
48 ADAMSB, NUNESJ M, PAGEM J, et al.Parkinson’s disease: a systemic inflammatory disease accompanied by bacterial inflammagens[J]Front Aging Neurosci, 2019, 210.
doi: 10.3389/fnagi.2019.00210
49 OLSENI, KELLD B, PRETORIUSE. Is porphyromonas gingivalis involved in Parkinson’s disease?[J]Eur J Clin Microbiol Infect Dis, 2020, 39( 11): 2013-2018.
doi: 10.1007/s10096-020-03944-2
50 FRISTERA, SCHMIDTC, SCHNEBLEN, et al.Phosphoinositide 3-kinase γ affects LPS-induced disturbance of blood-brain barrier via lipid kinase-independent control of cAMP in microglial cells[J]Neuromol Med, 2014, 16( 4): 704-713.
doi: 10.1007/s12017-014-8320-z
51 HERRERAA J, CASTAÑOA, VENEROJ L, et al.The single intranigral injection of LPS as a new model for studying the selective effects of inflammatory reactions on dopaminergic system[J]NeuroBiol Dis, 2000, 7( 4): 429-447.
doi: 10.1006/nbdi.2000.0289
52 RANJANR, ABHINAYA, MISHRAM. Can oral microbial infections be a risk factor for neurodegeneration? A review of the literature[J]Neurol India, 2018, 66( 2): 344.
doi: 10.4103/0028-3886.227315
53 DANIELYANL, SCHÄFERR, VON AMELN-MAYERHOFERA, et al.Intranasal delivery of cells to the brain[J]Eur J Cell Biol, 2009, 88( 6): 315-324.
doi: 10.1016/j.ejcb.2009.02.001
54 王 鹞, 吕慧欣, 杜留熠, 等. 软脑膜在外周炎症影响神经炎症过程中的作用[J]. 国际口腔医学杂志, 2019, 46(2): 223-227
WANG Yao, LYU Huixin, DU Liuyi, et al. Roles of leptomeninges in the effect of chronic peripheral inflammation on neuroinflammation[J]. International Journal of Stomatology, 2019, 46(2): 223-227. (in Chinese)
55 LIUY, WUZ, ZHANGX, et al.Leptomeningeal cells transduce peripheral macrophages inflammatory signal to microglia in reponse to porphyromonas gingivalis LPS[J]Mediators Inflamm, 2013, 407562.
doi: 10.1155/2013/407562
56 CHAOY, WONGS C, TANE K. Evidence of inflammatory system involvement in Parkinson’s disease[J]Biomed Res Int, 2014, 308654.
doi: 10.1155/2014/308654
57 CHENH, O’REILLYE J, SCHWARZSCHILDM A, et al.Peripheral inflammatory biomarkers and risk of Parkinson’s disease[J]Am J Epidemiol, 2007, 167( 1): 90-95.
doi: 10.1093/aje/kwm260
58 CAPURONL, MILLERA H. Immune system to brain signaling: neuropsychopharmacological implications[J]Pharmacol Ther, 2011, 130( 2): 226-238.
doi: 10.1016/j.pharmthera.2011.01.014
59 SVENSSONE, HORVÁTH-PUHÓE, THOMSENR W, et al.Vagotomy and subsequent risk of Parkinson’s disease[J]Ann Neurol, 2015, 78( 4): 522-529.
doi: 10.1002/ana.24448
60 BOTELHOJ, MASCARENHASP, MENDESJ J, et al.Network protein interaction in Parkinson’s disease and periodontitis interplay: a preliminary bioinformatic analysis[J]Genes, 2020, 11( 11): 1385.
doi: 10.3390/genes11111385
61 庞元捷, 吕 筠, 余灿清, 等. 多组学在慢性病病因学研究中的应用及其进展[J]. 中华流行病学杂志, 2021, 42(1): 1-9
PANG Yuanjie, LYU Jun, YU Canqing, et al. A multi-omics approach to investigate the etiology of non-communicable diseases: recent advance and applications[J]. Chinese Journal of Epidemiology, 2021, 42(1): 1-9. (in Chinese)
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