Journal of Prevention and Treatment for Stomatological Diseases ›› 2021, Vol. 29 ›› Issue (12): 828-835.DOI: 10.12016/j.issn.2096-1456.2021.12.005

• Clinical Study • Previous Articles     Next Articles

Changes and clinical significance of four biomarkers in gingival crevicular fluid after nonsurgical periodontal therapy

ZHANG Qian1(),CHEN Bin2,YAN Fuhua2()   

  1. 1. Department of Pediatric Dentistry, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, China
    2. Department of Periodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, China
  • Received:2021-04-22 Revised:2021-05-27 Online:2021-12-20 Published:2021-08-17
  • Contact: Fuhua YAN
  • Supported by:
    Cultivation Plan for the Establishment of Clinical Medicine Research Centers By The Provinces(2019060009);Key Project of Science and Technology Bureau of Jiangsu Province(BL2013002)



  1. 1.南京大学医学院附属口腔医院,南京市口腔医院儿童口腔科,江苏 南京(210008)
    2.南京大学医学院附属口腔医院,南京市口腔医院牙周病科,江苏 南京(210008)
  • 通讯作者: 闫福华
  • 作者简介:张倩,主治医师,博士,Email:
  • 基金资助:


Objective To study the changes in levels of interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-α), and alkaline phosphatase (ALP) in the gingival crevicular fluid (GCF) of patients with severe chronic periodontitis before and after nonsurgical periodontal therapy and to explore the relationship among the levels of these four biomarkers in GCF, their periodontal status and their clinical significance to evaluate the effect of nonsurgical periodontal therapy and periodontitis activity. Methods In total, 30 patients with severe chronic periodontitis were enrolled in a 1-year longitudinal pilot study (Chinese Clinical Trial Registry: ChiCTR-OCH-13004679). At baseline and 1, 3, 6, and 12 months after nonsurgical therapy, the periodontal clinical indicators plaque index (PLI), probing depth (PD), clinical attachment loss (CAL), sulcus bleeding index (SBI) were recorded. Filter paper strips were used to collect two deep-pocket (probing depth ≥ 6 mm) and two shallow-pocket (probing depth ≤ 4 mm) periodontal sites for each patient and weighed. The levels of interleukin IL-6, IL-10, TNF-α, and ALP in GCF were assessed using enzyme-linked immunosorbent assay. Meanwhile, 30 healthy sites of 15 subjects with healthy periodontium were used as the baseline controls for patients with severe chronic periodontitis. Results At the baseline, the TNF-α, ALP and IL-6 levels in GCF of the disease sites of patients with periodontitis were significantly higher than those in healthy periodontal sites of the control group (P < 0.001), and the levels of IL-10 were significantly lower than those in the control group (P < 0.001). In patients with severe chronic periodontitis, the levels of TNF-α, ALP and IL-6 in GCF at deep-pocket sites were significantly higher than those at shallow-pocket sites (P <0.001), and the IL-10 levels were significantly lower than those at shallow-pocket sites (P < 0.001). 1, 3, 6, and 12 months after nonsurgical treatment, the levels of TNF-α and ALP in GCF at the shallow- and deep-pocket sites in patients with chronic periodontitis significantly decreased, the level of IL-10 significantly increased (P < 0.005), and the level of IL-6 in GCF at the deep-pocket sites significantly decreased (P < 0.005). However, there was no significant difference in IL-6 level at shallow-pocket sites (P > 0.05). 1, 3, 6, and 12 months after nonsurgical treatment, the periodontal clinical indicators were improved compared with the baseline. In addition, there was a significant correlation between the levels of these four biomarkers and the periodontal clinical parameters (P < 0.05). During the two follow-up visits after nonsurgical periodontal therapy, the sites with more than 2-mm increase in attachment loss had significant differences in the levels of the four biomarkers in the GCF compared with the previous visit time (P < 0.005). Conclusion The detection of the levels of these four biomarkers in GCF has strong clinical significance for assessing the severity of periodontitis and the efficacy of nonsurgical periodontal therapy. Increased levels of TNF-α, ALP, and IL-6 and decreased IL-10 levels in GCF may indicate periodontitis progression at this site.

Key words: biomarkers, IL-10, TNF-α, IL-6, ALP, gingival crevicular fluid, nonsurgical periodontal therapy, severe chronic periodontitis, clinical trial


目的 研究牙周基础治疗前后重度慢性牙周炎患者不同牙位龈沟液(gingival crevicular fluid,GCF)中白细胞介素6(interleukin 6,IL-6)、白细胞介素10(interleukin 10,IL-10)、肿瘤坏死因子α(tumor necrosis α,TNF-α)、碱性磷酸酶(alkaline phosphatase,ALP)水平的变化,探讨以上4种生物标志物GCF水平与牙周状态的关系以及对牙周基础治疗效果、牙周炎活动性评估的临床意义。方法 共30例重度慢性牙周炎患者参与了为期1年的纵向试验研究(中国临床试验注册中心:ChiCTR-OCH-13004679)。在术前和基础治疗后1、3、6、12个月,记录牙周临床指标(菌斑指数、龈沟出血指数、探诊深度、临床附着丧失),并用滤纸条收集每例患者2个深袋牙位(探诊深度 ≥ 6 mm)和2个浅袋牙位(探诊深度 ≤ 4 mm)的GCF并称重,ELISA法测定GCF中IL-6、IL-10、TNF-α和ALP的水平。选取15名牙周健康者的30个健康牙位为重度慢性牙周炎患者的基线对照。结果 基线时,重度慢性牙周炎患者的疾病位点GCF中TNF-α、ALP、IL-6水平显著高于对照组的牙周健康位点(P<0.001),IL-10水平显著低于对照组(P < 0.001);重度慢性牙周炎患者深袋位点的GCF中TNF-α、ALP、IL-6水平显著高于浅袋位点(P<0.001);深袋位点IL-10水平显著低于浅袋位点(P < 0.001)。相较于基线,基础治疗后1、3、6、12个月,重度慢性牙周炎患者深袋、浅袋位点GCF中的TNF-α、ALP水平显著降低,IL-10水平显著升高(P<0.005),深袋位点GCF中IL-6水平显著降低(P < 0.005),浅袋位点的IL-6无统计学意义上的改变(P > 0.05)。治疗后1、3、6、12个月,4项牙周临床指标较基线均有改善,以上4种生物标志物水平与牙周临床指标之间均存在显著相关性,与IL-6、TNF-α、ALP呈正相关,与IL-10呈负相关(P < 0.05)。在基础治疗后的2次随访期间临床附着丧失增加超过2 mm的位点,GCF中4种生物标志物水平与上一次相比,差异有统计学意义(P<0.005)。结论 GCF中TNF-α、ALP、IL-6、IL-10这4种生物标志物的水平检测,对于判断牙周炎的严重程度、牙周基础治疗效果具有较强的临床意义。GCF中TNF-α、ALP、IL-6水平升高、IL-10水平降低可能预示着该位点出现牙周炎进展。

关键词: 生物标志物, 白细胞介素-10, 肿瘤坏死因子-α, 白细胞介素-6, 碱性磷酸酶, 龈沟液, 牙周基础治疗, 重度慢性牙周炎, 临床试验

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