伴阿尔茨海默病牙周炎患者血清Th17/Treg相关细胞因子水平变化研究

doi:10.3969/j.issn.1674-8115.2023.05.010

上海交通大学学报（医学版） ›› 2023, Vol. 43 ›› Issue (5): 600-605.doi: 10.3969/j.issn.1674-8115.2023.05.010

伴阿尔茨海默病牙周炎患者血清Th17/Treg相关细胞因子水平变化研究

谢欣宜(), 周薇, 邱澈, 沈慧, 宋忠臣()

上海交通大学医学院附属第九人民医院牙周病科，上海交通大学口腔医学院，国家口腔医学中心，国家口腔疾病临床医学研究中心，上海市口腔医学重点实验室，上海市口腔医学研究所，上海 200011

收稿日期:2022-11-22 接受日期:2023-04-28 出版日期:2023-05-28 发布日期:2023-07-11
通讯作者: 宋忠臣 E-mail:honeymelon2015@sjtu.edu.cn;szhongchen@sina.com
作者简介:谢欣宜（1996—），女，硕士生；电子信箱：honeymelon2015@sjtu.edu.cn。
基金资助:
国家自然科学基金(82071112);上海申康医院发展中心临床创新三年行动计划资助(SHDC2020CR5015)

Changes in serum Th17/Treg-related cytokine levels in periodontitis patients with Alzheimer′s disease

XIE Xinyi(), ZHOU Wei, QIU Che, SHEN Hui, SONG Zhongchen()

Department of Periodontology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China

Received:2022-11-22 Accepted:2023-04-28 Online:2023-05-28 Published:2023-07-11
Contact: SONG Zhongchen E-mail:honeymelon2015@sjtu.edu.cn;szhongchen@sina.com
Supported by:
National Natural Science Foundation of China(82071112);Clinical Research Plan of SHDC(SHDC2020CR5015)

摘要/Abstract

摘要：

目的·观察血清Th17/Treg水平的变化对阿尔茨海默病与牙周炎的影响。方法·纳入2020年6月—2021年12月就诊于上海交通大学医学院附属精神卫生中心老年科共18位伴阿尔茨海默病的牙周炎患者与同时期就诊于上海交通大学医学院附属第九人民医院共15位认知功能正常的牙周炎患者，检查并记录患者探诊深度（probing depth，PD）、附着丧失（clinical attachment loss，CAL）及探诊出血位点比例（percentage of bleeding on probing，BOP%）。使用酶联免疫吸附法检测血清中Th17相关细胞因子白细胞介素-6（interleukin-6，IL-6）、IL-17、IL-22及Treg相关细胞因子IL-4、IL-10、转化生长因子-β（transforming growth factor-β，TGF-β）水平。采用样本独立t检验比较2组牙周指标与细胞因子水平的差异，P<0.05表示差异具有统计学意义。结果·伴阿尔茨海默病的牙周炎患者PD（P=0.021）、CAL（P=0.023）及BOP%（P=0.018）均显著高于认知功能正常的牙周炎患者。伴阿尔茨海默病的牙周炎患者血清IL-6（P=0.010）、IL-17（P=0.022）、IL-22（P=0.031）水平均显著高于认知功能正常的牙周炎患者；同时，组中IL-4（P=0.002）及IL-10（P=0.049）、TGF-β（P=0.006）水平相较于认知功能正常的牙周炎患者显著降低。结论·伴阿尔茨海默病牙周炎患者的牙周状况比认知功能正常的牙周炎患者差，Th17相关促炎细胞因子升高，而Treg相关抗炎因子降低，说明牙周炎可能通过介导Th17/Treg相关的慢性炎症反应影响阿尔茨海默病的发生发展。

关键词: 阿尔茨海默病, 牙周炎, 细胞因子, Th17细胞, Treg细胞

Abstract:

Objective ·To observe the role of serum Th17/Treg levels in the correlation between Alzheimer′s disease and periodontitis. Methods ·Eighteen periodontitis patients with Alzheimer′s disease who visited the Department of Geriatric, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, and 15 periodontitis patients with normal cognitive function who visited the Department of Periodontology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from June 2020 to December 2021, were enrolled in this study. Probing depth (PD), clinical attachment loss (CAL) and percentage of bleeding on probing (BOP%) were examined and recorded. Serum levels of Th17-related cytokines interleukin-6 (IL-6), IL-17, and IL-22, Treg-related cytokines IL-4 and IL-10, and transforming growth factor-β (TGF-β) were measured by ELISA. The differences of periodontal status and cytokine levels were compared by using t-test. The difference was statistically significant when P<0.05. Results ·The PD (P=0.021), CAL (P=0.018) and BOP% (P=0.018) were significantly higher in the periodontitis patients with Alzheimer′s disease than those in periodontitis patients with normal cognitive function. The serum IL-6 (P=0.010), IL-17 (P=0.022) and IL-22 (P=0.031) levels were significantly higher in the periodontitis patients with Alzheimer′s disease than those in periodontitis patients with normal cognitive function, while the levels of IL-10 (P=0.049), IL-4 (P=0.002) and TGF-β (P=0.006) in the periodontitis patients with Alzheimer′s disease were significantly lower compared with those in periodontitis patients with normal cognitive function. Conclusion ·The periodontal condition of periodontitis patients with Alzheimer′s disease is worse compared to that of periodontitis patients with normal cognitive function. The expression of Th17-related pro-inflammatory cytokines is elevated, while the expression of Treg-related anti-inflammatory factors is decreased. Thus, periodontitis may affect the development of Alzheimer′s disease by mediating Th17/Treg-related chronic inflammatory responses.

Key words: Alzheimer′s disease, periodontal disease, cytokins, Th17 cell, Treg cell

中图分类号:

R781.4

谢欣宜, 周薇, 邱澈, 沈慧, 宋忠臣. 伴阿尔茨海默病牙周炎患者血清Th17/Treg相关细胞因子水平变化研究[J]. 上海交通大学学报（医学版）, 2023, 43(5): 600-605.

XIE Xinyi, ZHOU Wei, QIU Che, SHEN Hui, SONG Zhongchen. Changes in serum Th17/Treg-related cytokine levels in periodontitis patients with Alzheimer′s disease[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(5): 600-605.

图/表 3

表1 患者牙周状况比较

Tab 1 Periodontal parameters of the two groups

Index	Group		t value	P value
Index	AD+CP (n=18)	CP (n=15)	t value	P value
PD/mm	2.82±0.04	2.25±0.03	2.436	0.021
CAL/mm	3.92±0.08	2.90±0.06	2.396	0.023
BOP%	61.94±1.39	40.97±1.51	2.497	0.018

图1 2组患者血清Th17相关细胞因子水平的比较Note： A. IL-6. B. IL-17. C. IL-22.Compared with CP group, ①P=0.010, ②P=0.022, ③P=0.031.

Fig 1 Comparison of serum Th17-related cytokine levels between the two groups

图2 2组患者血清Treg相关细胞因子水平的比较Note： A. IL-4. B. IL-10. C. TGF-β. Compared with CP group. ①P=0.002, ②P=0.049, ③P=0.006.

Fig 2 Comparison of serum Treg-related cytokine levels between the two groups

参考文献 30

1	孟焕新. 牙周病学[M]. 5版. 北京: 人民卫生出版社, 2020:1-2.
	MENG H X. Periodontology [M]. Fifth edition. Beijing: People′s Medical Publishing House, 2020:1-2
2	TELES F, WANG Y, HAJISHENGALLIS G, et al. Impact of systemic factors in shaping the periodontal microbiome[J]. Periodontol, 2000, 2021,85(1): 126-160.
3	ELWISHAHY A, ANTIA K, BHUSARI S, et al. Porphyromonas gingivalis as a risk factor to alzheimer′s disease: a systematic review[J]. J Alzheimers Dis Rep, 2021, 5(1): 721-732.
4	KAMER A R, CRAIG R G, NIEDERMAN R, et al. Periodontal disease as a possible cause for Alzheimer′s disease[J]. Periodontol 2000, 2020, 83(1): 242-271.
5	BREIJYEH Z, KARAMAN R. Comprehensive review on alzheimer′s disease: causes and treatment[J]. Molecules, 2020, 25(24): 5789
6	HAJISHENGALLIS G, CHAVAKIS T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities[J]. Nat Rev Immunol, 2021, 21(7): 426-440.
7	ZHANG L P, GAO L, XU C R, et al. Porphyromonas gingivalis lipopolysaccharide promotes T-helper 17 cell differentiation from human CD4⁺ naïve T cells via toll-like receptor-2 in vitro[J]. Arch Oral Biol, 2019, 107: 104483.
8	LEE G R. The balance of Th17 versus treg cells in autoimmunity[J]. Int J Mol Sci, 2018, 19(3): 730.
9	JIA L, WU R Q, HAN N N, et al. Porphyromonas gingivalis and Lactobacillus rhamnosus GG regulate the Th17/Treg balance in colitis via TLR4 and TLR2[J]. Clin Transl Immunology, 2020, 9(11): e1213.
10	LEAL-LASARTE M, MANNINI B, CHITI F, et al. Distinct responses of human peripheral blood cells to different misfolded protein oligomers[J]. Immunology, 2021, 164(2): 358-371.
11	CATON J G, ARMITAGE G, BERGLUNDH T, et al. A new classification scheme for periodontal and peri-implant diseases and conditions-Introduction and key changes from the 1999 classification[J]. J Clin Periodontol, 2018, 45(Suppl 20): S1-S8.
12	冯希平. 中国居民口腔健康状况: 第四次中国口腔健康流行病学调查报告[C]//2018年中华口腔医学会第十八次口腔预防医学学术年会论文汇编. 西安, 2018: 13-14.
	FENG X P. Oral health status of Chinese residents—report of the fourth Chinese oral health epidemiological survey: the eighteenth annual academic conference on preventive dentistry of the Chinese dental association, 2018, Xi′an, China, 2018: 13-14.
13	FI C, WO W. Periodontal disease and systemic diseases: an overview on recent progresses[J]. J Biol Regul Homeost Agents, 2021, 35(1 Suppl. 1): 1-9.
14	KAPILA Y L. Oral health′s inextricable connection to systemic health: special populations bring to bear multimodal relationships and factors connecting periodontal disease to systemic diseases and conditions[J]. Periodontol, 2000, 2021, 87(1): 11-16.
15	KALHAN A C, WONG M L, ALLEN F, et al. Periodontal disease and systemic health: an update for medical practitioners[J]. Ann Acad Med Singap, 2022, 51(9): 567-574.
16	任汝静, 殷鹏, 王志会, 等. 中国阿尔茨海默病报告2021[J]. 诊断学理论与实践, 2021, 20(4): 317-337.
	REN R J, YIN P, WANG Z H, et al. China Alzheimer disease report 2021[J]. J Diagn Concepts Pract, 2021, 20(4): 317-337.
17	LAUGISCH O, JOHNEN A, BUERGIN W, et al. Oral and periodontal health in patients with Alzheimer′s disease and other forms of dementia-A cross-sectional pilot study[J]. Oral Health Prev Dent, 2021, 19(1): 255-261.
18	BEYDOUN M A, BEYDOUN H A, HOSSAIN S, et al. Clinical and bacterial markers of periodontitis and their association with incident all-cause and alzheimer′s disease dementia in a large national survey[J]. J Alzheimers Dis, 2020, 75(1): 157-172.
19	TSUNEISHI M, YAMAMOTO T, YAMAGUCHI T, et al. Association between number of teeth and Alzheimer′s disease using the National Database of Health Insurance Claims and Specific Health Checkups of Japan[J]. PLoS One, 2021, 16(4): e0251056.
20	SCHERER R X, SCHERER W J. U.S. state correlations between oral health metrics and Alzheimer′s disease mortality, prevalence and subjective cognitive decline prevalence[J]. Sci Rep, 2020, 10(1): 20962.
21	JUNGBAUER G, STÄHLI A, ZHU X L, et al. Periodontal microorganisms and Alzheimer disease:a causative relationship?[J]. Periodontol, 2000, 2022, 89(1): 59-82.
22	SADRAMELI M, BATHINI P, ALBERI L. Linking mechanisms of periodontitis to Alzheimer′s disease[J]. Curr Opin Neurol, 2020, 33(2): 230-238.
23	ZHANG W Q, LIU X, ZHU Y C, et al. Transcriptional and posttranslational regulation of Th17/Treg balance in health and disease[J]. Eur J Immunol, 2021, 51(9): 2137-2150.
24	DENG J W, LU C T, ZHAO Q T, et al. The Th17/Treg cell balance: crosstalk among the immune system, bone and microbes in periodontitis[J]. J Periodontal Res, 2022, 57(2): 246-255.
25	ZHANG X, ZHANG X, QIU C, et al. The imbalance of Th17/Treg via STAT3 activation modulates cognitive impairment in P. gingivalis LPS-induced periodontitis mice[J]. J Leukoc Biol, 2021, 110(3): 511-524.
26	SHEN X N, NIU L D, WANG Y J, et al. Inflammatory markers in Alzheimer′s disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies[J]. J Neurol Neurosurg Psychiatry, 2019, 90(5): 590-598.
27	YAN X Z, LAI L J, AO Q, et al. Interleukin-17A in alzheimer′s disease: recent advances and controversies[J]. Curr Neuropharmacol, 2022, 20(2): 372-383.
28	WANG X H, ZHANG M, LIU H F. LncRNA17A regulates autophagy and apoptosis of SH-SY₅Y cell line as an in vitro model for Alzheimer′s disease[J]. Biosci Biotechnol Biochem, 2019, 83(4): 609-621.
29	THOMAS A J, HAMILTON C A, DONAGHY P C, et al. Prospective longitudinal evaluation of cytokines in mild cognitive impairment due to AD and Lewy body disease[J]. Int J Geriatr Psychiatry, 2020, 35(10): 1250-1259.
30	GAO S S, CHU C H, YOUNG F Y F. Oral health and care for elderly people with alzheimer′s disease[J]. Int J Environ Res Public Health, 2020, 17(16): 5713.

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伴阿尔茨海默病牙周炎患者血清Th17/Treg相关细胞因子水平变化研究

Changes in serum Th17/Treg-related cytokine levels in periodontitis patients with Alzheimer′s disease

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