国际口腔医学杂志

国际口腔医学杂志 ›› 2019, Vol. 46 ›› Issue (3): 308-315.doi: 10.7518/gjkq.2019042

• 综述 • 上一篇    下一篇

口腔龈沟液生物标志物的检测分析现状及临床应用前景展望

胡竹林,赵诣,李茵()   

  1. 首都医科大学附属北京口腔医院修复科 北京 100050
  • 收稿日期:2018-08-10 修回日期:2019-01-21 出版日期:2019-05-01 发布日期:2019-06-05
  • 通讯作者: 李茵
  • 作者简介:胡竹林,医师,硕士,Email：hzl2016lf@163.com
  • 基金资助:
    国家自然科学基金(81171004);北京自然科学基金(7123214);北京市科技新星项目(Z131107000413040);北京市医院管理局临床技术创新项目(XMLX201402)

Analysis status and clinical application prospect of biomarkers in oral gingival crevicular fluid

Zhulin Hu,Yi Zhao,Yin Li()   

  1. Dept. of Prosthodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
  • Received:2018-08-10 Revised:2019-01-21 Online:2019-05-01 Published:2019-06-05
  • Contact: Yin Li
  • Supported by:
    This study was supported by National Natural Science Foundation of China(81171004);Beijing Natural Science Foundation(7123214);Beijing Science and Technology New Star Project(Z131107000413040);Clinical Technical Innovation Project of Beijing Hospital Administration(XMLX201402)

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摘要：

龈沟液是存在于牙周龈沟或牙周袋内的组织渗透液,其含量和成分变化与牙周组织健康关系密切。目前研究热点主要集中在寻找比较可靠的高灵敏度和高特异性龈沟液生物标志物以及简单易于操作的临床椅旁检测技术,以期实现对牙周组织不良反应和感染炎症的早期发现、干预和治疗。龈沟液检测具有很大的临床应用潜力,将给临床诊断带来更加客观的量化证据。本文对近年来龈沟液主要生物标志物成分分析、检测技术以及临床应用前景作一综述。

关键词: 牙周病, 龈沟液, 生物标志物, 检测技术, 临床应用

Abstract:

Gingival crevicular fluid is a tissue transudate present in the periodontal gingival sulcus or a periodontal pocket, and its amount and composition are closely related to the state of periodontal tissues. Current research focuses on finding reliable, high-sensitivity and high-specificity gingival crevicular fluid biomarkers and convenient clinical chair-side detection technology to achieve the early detection, intervention and treatment of the adverse reactions and inflammation of periodontal tissues. Gingival crevicular fluid detection shows great potential for clinical application and likely provides objective quantitative evidence for clinical diagnosis. Thus, this review summarises the recent studies on the biomarker composition, detection technology and clinical application prospect of gingival crevicular fluid.

Key words: periodontitis, gingival crevicular fluid, biomarker, detection technique, clinical application

中图分类号: 

  • R781.4

表 1

牙周炎症状态下龈沟液主要成分的分析"

分类 标志物名称 含量变化 检测方法 参考文献
酶类 碱性磷酸酶（alkaline phosphatase,ALP） 增加 酶联免疫吸附法（enzyme linked immunosor- [7-8]
bent assay,ELISA）;荧光测定法
天冬氨酸转氨酶（aspartate aminotransferase,AST） 增加 干化学法 [9]
β-葡萄糖醛酸酶（β-glucuronidase,β-G） 增加 分光光度法 [10]
弹性蛋白酶（elastase,EA） 增加 荧光测定法 [11]
组织蛋白酶B（cathepsin B,CTSB） 增加 荧光测定法 [12]
组织蛋白酶K（cathepsin K,CTSK） 增加 ELISA [13]
基质金属蛋白酶-1（matrix metalloproteinase,MMP-1） 增加 ELISA [14]
基质金属蛋白酶-2（matrix metalloproteinase,MMP-2） 增加 明胶酶谱法 [15]
基质金属蛋白酶-3（matrix metalloproteinase,MMP-3） 增加 ELISA [16-17]
基质金属蛋白酶-8 （matrix metalloproteinase,MMP-8） 增加 ELISA [15,18-20]
基质金属蛋白酶-9 （matrix metalloproteinase,MMP-9） 增加 ELISA;明胶酶谱法 [15,18,20]
基质金属蛋白酶-13（matrix metalloproteinase,MMP-13） 增加 ELISA [16]
基质金属蛋白酶组织抑制剂-1（tissue inhibitor of metallo pro- 减少 ELISA [14,17]
teinase-1,TIMP-1）
髓过氧化物酶（myeloperoxidase,MPO） 增加 ELISA [15,18]
炎症介 白细胞介素-1β（interleukin-1β,IL-1β） 增加 ELISA;液相芯片 [21-23]
质类 白细胞介素-6（interleukin-6,IL-6） 增加 ELISA;液相芯片 [8,15,22,24]
白细胞介素-8（interleukin-8,IL-8） 增加 ELISA;液相芯片 [22-23,25]
肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α） 增加 ELISA;液相芯片 [8,22-23]
干扰素-γ（interferon-γ,IFN-γ） 增加 液相芯片 [26]
前列腺素E2（prostaglandin E2,PGE2） 增加 ELISA [27]
白三烯 B4（leukotriene B4,LTB4） 增加 酶免疫法 [28]
单核细胞趋化蛋白-1（monocyte chemotactic protein-1,MCP- 增加 ELISA [29-30]
1）
调节活化正常T细胞表达与分泌的趋化因子（regulated upon 增加 液相芯片 [31]
activation normal T-cell expressed and secreted,RANTES）
C-反应蛋白（C-reactive protein,CRP） 增加 ELISA [8]
乳铁蛋白（lactoferrin,LF） 增加 ELISA [32]
P物质（substance-P,SP） 增加 放射免疫法 [33]
免疫球蛋白-G（immunoglobulin G,IgG） 增加 ELISA [34]
组织破 硫酸软骨素（chondroitin sulfate,CS） 增加 ELISA [7]
坏产物 羟脯氨酸（hydroxyproline,Hyp） 增加 生物化学法 [35]
骨钙素（osteocalcin,OC） 增加 电化学发光法 [36]
分类 标志物名称 含量变化 检测方法 参考文献
骨桥蛋白（osteopontin,OPN） 增加 酶免疫法 [37]
骨结合蛋白 增加 斑点印迹法 [38]
核因子-κB受体活化因子配体（receptor activator of nuclear 增加 ELISA [39-40]
factor-κB ligand,RANKL）
骨保护素（osteoclastogenesis inhibitory factor,OPG） 减少 ELISA [39-40]
Ⅰ型胶原交联羧基端肽（type I collagen cross-linked carboxyl 增加 放射免疫法;酶免疫法 [41-42]
terminal telopeptide,ICTP）
钙卫蛋白 增加 ELISA [43]

表 2

龈沟液炎症标志物的常用检测方法"

检测方法 优势 劣势
分光光度法 操作简便快速,成本低,应用广泛 对样品纯度要求高;灵敏度和准确度不高
荧光测定法 特异性和灵敏度较高 应用具有局限性;操作复杂;耗时长,易受反应温度和时间等的影响
放射免疫法 特异性和灵敏度较高,简便易行,用样量少等 有时会出现交叉反应、假阳性反应,组织样品处理不够迅速,不能灭
活降解酶和盐及pH有时会影响结果等;放射性物质对操作人员有危
害,且实验后不易处理
免疫印迹法 分析容量大、敏感度高、特异性强等优点,是检测蛋 不能准确定量,且检测数量有限
白质特性、表达与分布的一种最常用的方法
ELISA 简单,快速,灵敏度高,特异性强;所用设备简单, 每次只能检测一种目标分子
无污染,易于普及;试剂稳定,便于保存
液相芯片技术 简便,快速,高通量,高效率,灵敏度高,特异性强, 成本较高
重复性好

表 3

龈沟液标志物检测的临床应用前景"

应用 目的
牙周炎诊断 1）疾病风险评估,早期诊断和严重程度诊断;2）指导临床用药;3）指导治疗计划制定;4）监测预后情况
种植体周围炎诊断 1）监测种植效果;2）种植体周围炎早期诊断及与种植体黏膜炎鉴别
修复体基牙牙周状态评价 1）确定修复时机;2）指导修复材料和修复方式的应用及效果评价;3）对修复体造成的牙周炎进行早期诊断
正畸矫治牙牙周状态评价 1）指导正畸时机;2）评估治疗效果;3）对正畸过程中应力或局部刺激导致的牙周组织破坏进行早期诊断
系统性疾病与牙周关系评价 1）辅助诊断系统性疾病或评价其预后;2）对由系统性疾病造成的牙周炎作出鉴别
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