国际口腔医学杂志

国际口腔医学杂志 ›› 2020, Vol. 47 ›› Issue (5): 530-537.doi: 10.7518/gjkq.2020024

• 论著 • 上一篇    下一篇

慢性牙周炎对c57小鼠认知能力的影响

童钰鑫1,2,3(),肖新莉4,安莹3,张佳喻1,2,5,石旭妍1,2,5,王旭1,2,5,陈悦1,2,5()   

  1. 1.陕西省颅颌面精准医学研究重点实验室 西安 710032
    2.陕西省牙颌面疾病临床研究中心 西安 710032
    3.军事口腔医学国家重点实验室,口腔疾病国家临床医学研究中心,陕西省口腔生物工程技术研究中心,空军军医大学口腔医院牙周病科 西安 710032
    4.西安交通大学医学院 西安 710061
    5.西安交通大学口腔医院牙周黏膜科 西安 710004
  • 收稿日期:2019-12-20 修回日期:2020-04-17 出版日期:2020-09-01 发布日期:2020-09-16
  • 通讯作者: 陈悦
  • 作者简介:童钰鑫,住院医师,硕士,Email: wotyx101@163.com
  • 基金资助:
    国家自然科学基金青年项目(81700971);陕西省自然科学基础研究项目(2018JM7116)

Influence of c57 mouse periodontitis model on cognitive ability

Tong Yuxin1,2,3(),Xiao Xinli4,An Ying3,Zhang Jiayu1,2,5,Shi Xuyan1,2,5,Wang Xu1,2,5,Chen Yue1,2,5()   

  1. 1.Key Laboratory of Shanxi Province for Craniofacial Precision Medicine Research, Xi’an 710032, China
    2.Clinical Research Center of Shanxi Province for Dental and Maxillofacial Diseases, Xi’an 710032, China
    3.State Key Laboratory of Millitary Stomatology & National Clinical Research Center for Oral Disease & Shanxi Engineering Research Center for Dental Materials and Advanced Manufacture & Dept. of Periodontology, Stomatology Hospital of Air Force Military Medical University, Xi’an 710032, China
    4.Medical School of Xi’an Jiaotong University, Xi’an 710061, China
    5.Dept. of Periodontology, Stomatological Hospital, Xi’an Jiaotong University, Xi’an 710004, China
  • Received:2019-12-20 Revised:2020-04-17 Online:2020-09-01 Published:2020-09-16
  • Contact: Yue Chen
  • Supported by:
    National Natural Science Foundation of China Youth Project(81700971);Natural Science Basic Research Program of Shanxi(2018JM7116)

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摘要：

目的 通过口腔局部注射脂多糖建立慢性牙周炎动物模型,研究慢性牙周炎对c57小鼠认知学习能力的影响。方法 选择同月龄雌性c57小鼠20只,随机分为实验组、对照组。实验组使用微量注射器在牙周局部注射脂多糖,建立慢性牙周炎动物模型。建模结束后进行Morris水迷宫行为学检测,取材观察海马CA3区尼氏体、神经元状态、牙槽骨吸收情况,采用酶联免疫吸附测定法检测海马及血清中白细胞介素（IL）-1β含量,采用SPSS 18.0软件对数据进行统计分析。结果 在Morris水迷宫定位航行实验中,2个组潜伏期随着实验天数的增加逐渐减少,趋触性降低;与对照组相比,实验组潜伏期显著增长（P<0.000 1）,趋触性增加（P<0.000 1）,海马内CA3区神经元数量显著减少（P=0.001）。实验组血清IL-1β含量显著高于对照组（P=0.007）。结论 2个组小鼠均具有学习记忆能力,慢性牙周炎能够损害小鼠的学习能力,可能与炎症机制相关,但具体机制仍需进一步研究。

关键词: 脂多糖, 牙周炎, 阿尔兹海默症, 认知障碍

Abstract:

Objective This work aimed to establish a lipopolysaccharide (LPS)-induced animal model of periodontitis and observe the influence of LPS injection on the behaviour of c57 mice. Methods Twenty female c57 mice were ran-domly divided into two groups: blank control and experimental periodontitis groups. Mice in the experimental group were injected with Escherichia coli LPS by a microsyringe. Morris water maze (MWM) test was performed to assess the learning and memory ability of mice after 39 days. The expression levels of the proinflammatory cytokine interleukin (IL)-1β in mouse hippocampus tissues and serum were determined by enzyme-linked immunosorbent assay. Nissl body and neuron status in the CA3 area of the brain hippocampus were observed by Nissl staining, and alveolar bone resorption was evaluated by haematoxylin and eosin staining. Results In MWM positioning navigation experiment, the latency and thigmotaxis of both groups decreased gradually. The latency and thigmotaxis of the experimental group in the MWM experiment increased significantly compared with the control group (P<0.000 1). The number of neurons in the CA3 area of the experimental group mice increased significantly compared with the control group (P=0.001). The serum IL-1β content was higher in the experimental group than in the blank control group (P=0.007). Conclusion Long-term injection of low-dose LPS can induce bone loss and may cause cognitive impairment to c57 mice.

Key words: lipopolysaccharide, periodontitis, Alzheimer’s disease, cognitive impairment

中图分类号: 

  • R781.4+2

图 1

不同组别小鼠水迷宫潜伏期结果"

图 2

不同组别小鼠水迷宫趋触性结果"

图 3

小鼠海马尼氏染色形态观察 A、C:实验组;B、D:对照组;A、B:放大10倍;C、D:放大40倍。"

图 4

慢性牙周炎动物模型MicroCT三维重建图 A:对照组;B:实验组。a:第一磨牙腭侧中间位点牙槽骨丧失垂直高度;b:第一磨牙腭侧近中位点牙槽骨丧失垂直高度;c:第二磨牙腭侧远中位点牙槽骨丧失垂直高度;d:第二磨牙腭侧中间位点牙槽骨丧失垂直高度。"

图 5

HE染色观察牙槽骨吸收情况 A、B:对照组;C、D:实验组;A、C:放大10倍;B、D:放大20倍。"

[1] Ganesh P, Karthikeyan R, Muthukumaraswamy A, et al. A potential role of periodontal inflammation in Alzheimer’s disease: a review[J]. Oral Health Prev Dent, 2017,15(1):7-12.
pmid: 28232969
[2] Teixeira FB, Saito MT, Matheus FC, et al. Periodon-titis and Alzheimer’s disease: a possible comorbidity between oral chronic inflammatory condition and neuroinflammation[J]. Front Aging Neurosci, 2017,9:327.
doi: 10.3389/fnagi.2017.00327 pmid: 29085294
[3] Erickson MA, Banks WA. Neuroimmune axes of the blood-brain barriers and blood-brain interfaces: bases for physiological regulation, disease states, and phar-macological interventions[J]. Pharmacol Rev, 2018,70(2):278-314.
pmid: 29496890
[4] 杨文璐, 刘凤侠, 张小慢. 轻度认知障碍转化阿尔兹海默病影像预测研究[J]. 安徽大学学报(自然科学版), 2014,38(2):90-95.
Yang WL, Liu FX, Zhang XM . The research on ima-ging prediction of MCI convert to AD[J]. J Anhui Univ Nat Sci, 2014,38(2):90-95.
[5] Gatz M, Mortimer JA, Fratiglioni L, et al. Potentially modifiable risk factors for dementia in identical twins[J]. Alzheimers Dement, 2006,2(2):110-117.
pmid: 19595867
[6] Lane CA, Hardy J, Schott JM. Alzheimer’s disease[J]. Eur J Neurol, 2018,25(1):59-70.
doi: 10.1111/ene.13439 pmid: 28872215
[7] Jourdain ML, Pierrard L, Kanagaratnam L, et al. Antimicrobial peptide gene expression in perio-dontitis patients: a pilot study[J]. J Clin Periodontol, 2018,45(5):524-537.
pmid: 29446150
[8] 陈悦. 黄芩苷抑制牙周炎牙槽骨吸收的作用及机理研究[D]. 西安: 第四军医大学, 2008.
Chen Y . Study on the effects and mechanisms of baicalin on alveolar bone resorption[D]. Xi’an: The Fourth Military Medical University, 2008.
[9] Kinane DF, Stathopoulou PG, Papapanou PN. Perio-dontal diseases[J]. Nat Rev Dis Primers, 2017,3:17038.
pmid: 28805207
[10] Liu RK, Desta T, Raptis M, et al. P. gingivalis and E. coli lipopolysaccharides exhibit different systemic but similar local induction of inflammatory markers[J]. J Periodontol, 2008,79(7):1241-1247.
doi: 10.1902/jop.2008.070575 pmid: 18597607
[11] Moriyama H, Ukai T, Hara Y. Interferon-gamma production changes in parallel with bacterial lipopoly- saccharide induced bone resorption in mice: an im-munohistometrical study[J]. Calcif Tissue Int, 2002,71(1):53-58.
pmid: 12043012
[12] Fox M, Knorr DA, Haptonstall KM. Alzheimer’s disease and symbiotic microbiota: an evolutionary medicine perspective[J]. Ann N Y Acad Sci, 2019,1449(1):3-24.
pmid: 31180143
[13] Monroe TB, Gibson SJ, Bruehl SP, et al. Contact heat sensitivity and reports of unpleasantness in communicative people with mild to moderate cogni-tive impairment in Alzheimer’s disease: a cross-sec-tional study[J]. BMC Med, 2016,14:74.
pmid: 27164846
[14] 邓必高, 但伶, 黄燕, 等. 异丙酚对大鼠内毒素脑损伤STAT3表达的影响[J]. 世界科技研究与发展, 2012,34(1):137-139, 162.
Deng BG, Dan L, Huang Y , et al. Effects of propofol treatment on expression of STAT3 in brain tissue in rats with LPS-induced brain injury[J]. World Sci-Tech Res Dev, 2012,34(1):137-139, 162.
[15] Rebola N, Carta M, Mulle C. Operation and plas-ticity of hippocampal CA3 circuits: implications for memory encoding[J]. Nat Rev Neurosci, 2017,18(4):208-220.
doi: 10.1038/nrn.2017.10 pmid: 28251990
[16] 段海燕, 章锦才, 张蕴惠. IL-1基因多态性与牙周炎关系的研究[J]. 华西口腔医学杂志, 2002,20(1):48-51.
Duan HY, Zhang JC, Zhang YH . The association between IL-1 gene polymorphisms and susceptibility to severe periodontitis[J]. West China J Stomatol, 2002,20(1):48-51.
[17] Minter MR, Taylor JM, Crack PJ. The contribution of neuroinflammation to amyloid toxicity in Alzhei-mer’s disease[J]. J Neurochem, 2016,136(3):457-474.
doi: 10.1111/jnc.13411 pmid: 26509334
[18] Vom Berg J, Prokop S, Miller KR, et al. Inhibition of IL-12/IL-23 signaling reduces Alzheimer’s disease-like pathology and cognitive decline[J]. Nat Med, 2012,18(12):1812-1819.
pmid: 23178247
[19] Babcock AA, Ilkjær L, Clausen BH, et al. Cytokine-producing microglia have an altered beta-amyloid load in aged APP/PS1 Tg mice[J]. Brain Behav Immun, 2015,48:86-101.
pmid: 25774009
[20] Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases[J]. Blood, 2011,117(14):3720-3732.
doi: 10.1182/blood-2010-07-273417
[21] Cherry JD, Olschowka JA, O’Banion MK. Arginase 1+ microglia reduce Aβ plaque deposition during IL-1β-dependent neuroinflammation [J]. J Neuroin-flammation, 2015,12:203.
[22] Matousek SB, Ghosh S, Shaftel SS, et al. Chronic IL-1β-mediated neuroinflammation mitigates amyloid pathology in a mouse model of Alzheimer’s disease without inducing overt neurodegeneration[J]. J Neuroimmune Pharmacol, 2012,7(1):156-164.
doi: 10.1007/s11481-011-9331-2 pmid: 22173340
[23] 王秀秀. 水合氯醛对大鼠认知功能、海马Bcl-2、Bax蛋白表达的影响[D]. 南宁: 广西医科大学, 2017.
Wang XX . Effects of chloral hydrate on cognitive function the expression of Bcl-2 and Bax proteins in hippocampus in rats[D]. Nanning: Guangxi Medical University, 2017.
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