慢性牙周炎合并2型糖尿病患者龈沟液miR-21、miR-34a表达水平与牙周指标和Th1/Th2/Th17失衡的关系研究

Relationship Study between miR-21 and miR-34a Expression Levels in Gingival Sulcus Fluid and Periodontal Indicators and Th1/Th2/Th17 Imbalance in Patients with Chronic Periodontitis Complicated with Type 2 Diabetes Mellitus

目的:探讨慢性牙周炎(CP)合并2型糖尿病(T2DM)患者龈沟液微小核糖核酸(mi R)-21、mi R-34a表达水平与牙周指标和辅助性T细胞(Th)1/Th2/Th17失衡的关系。方法:选取2020年3月~2022年3月首都医科大学附属北京世纪坛医院口腔科收治的114例CP患者,根据是否合并T2DM分为CP合并T2DM组36例和单纯CP组78例,另选取60名健康体检者为对照组。对比三组牙周指标、龈沟液mi R-21、mi R-34a表达和外周血Th1、Th2、Th17、Th1/Th2/Th17、血清Th1、Th2、Th17相关细胞因子水平,采用Spearman相关性分析CP合并T2DM患者龈沟液mi R-21、mi R-34a表达与牙周指标和外周血Th1、Th2、Th17、Th1/Th2/Th17及其相关细胞因子水平的相关性。采用Pearson/Spearman相关性分析CP合并T2DM患者牙周指标与外周血Th1、Th2、Th17、Th1/Th2/Th17及其相关细胞因子水平的相关性。结果:对照组、单纯CP组、CP合并T2DM组菌斑指数(PLI)、牙龈出血指数(BI)、附着丧失(AL)、探诊深度(PD)依次增加,龈沟液mi R-21和外周血Th2及血清白细胞介素(IL)-2、干扰素-γ(INF-γ)依次降低,龈沟液mi R-34a和外周血Th1、Th17、Th1/Th2/Th17及血清IL-4、IL-10、IL-17、肿瘤坏死因子-α(TNF-α)依次升高(P<0.05)。Spearman相关性分析显示,CP合并T2DM患者龈沟液mi R-21表达与PLI、BI、AL、PD和外周血Th1、Th17、Th1/Th2/Th17及血清IL-4、IL-10、IL-17、TNF-α呈负相关,与外周血Th2和血清IL-2、INF-γ呈正相关(P<0.05);而mi R-34a则与之相反。Pearson/Spearman相关性分析显示,CP合并T2DM患者PLI、BI、AL、PD与外周血Th1、Th17、Th1/Th2/Th17和血清IL-4、IL-10、IL-17、TNF-α呈正相关,与外周血Th2和血清IL-2、INF-γ呈负相关(P<0.05)。结论:CP合并T2DM患者龈沟液mi R-21低表达和mi R-34a高表达,与牙周状况差有关,可能通过调节Th1/Th2/Th17失衡参与CP合并T2DM进展。

Objective:To investigate the relationship between the microribonucleic acid(miR)-21 and miR-34a expression levels in gingival sulcus fluid and the periodontal indicators and helper T cells(Th)1/Th2/Th17 imbalance in patients with chronic periodontitis(CP)complicated with type 2 diabetes mellitus(T2DM).Methods:114 patients with CP who were admitted to Department of Stomatology,Beijing Shijitan Hospital Affiliated to Capital Medical University from March 2020 to March 2022 were selected,according to whether they had T2DM,patients were divided into CP complicated with T2DM group with 36 cases and CP alone group with 78 cases.Another 60 healthy subjects were selected as control group.The periodontal indexes,miR-21 and miR-34a expression in gingival sulcus fluid and Th1,Th2,Th17,Th1/Th2/Th17,serum Th1,Th2,and Th17 related cytokines levels in the three groups were compared.Spearman correlation was used to analyze the correlation between the miR-21 and miR-34a expression in gingivicular sulcus fluid of patients with CP complicated with T2DM and the periodontal indicators,Th1,Th2,Th17,Th1/Th2/Th17 and their related cytokines levels in peripheral blood.Pearson/Spearman correlation was used to analyze the correlation between periodontal indicators and Th1,Th2,Th17,Th1/Th2/Th17 in peripheral blood and related cytokines levels in patients with CP complicated with T2DM.Results:Plaque index(PLI),gingival bleeding index(BI),attachment loss(AL),probing depth(PD)increased sequentially in the control group,CP alone group,CP complicated with T2DM group,and both miR-21 in gingival sulcus fluid and Th2 in peripheral blood and serum Interleukin(IL)-2 and Interferon-γ(INF-γ)decreased sequentially,miR-34a in gingival sulcus fluid and Th1,Th17,Th1/Th2/Th17 in peripheral blood and serum IL-4,IL-10,IL-17,Tumor necrosis factor-α(TNF-α)elevated sequentially(P<0.05).Spearman correlation analysis showed that miR-21 expression in gingival sulcus fluid of patients with CP complicated with T2DM was negatively correlated with PLI,BI,Al,PD and peripheral blood Th1,Th17,Th1/Th2/Th17 as well as serum IL-4,IL-10,IL-17,TNF-α,and was positively correlated with peripheral Th2 and serum IL-2,INF-γ(P<0.05);while miR-34a did the opposite.Pearson/Spearman correlation analysis showed that PLI,BI,Al,PD were positively correlated with peripheral blood Th1,Th17,Th1/Th2/Th17 and serum IL-4,IL-10,IL-17,TNF-αin patients with CP complicated with T2DM,and were negatively correlated with Th2 in peripheral blood and serum IL-2 and INF-γ(P<0.05).Conclusion:The low expression of miR-21 and high expression of miR-34a in gingival sulcus fluid of patients with CP complicated with T2DM are related to poor periodontal status,which may be involved in the progression of patients with CP complicated with T2DM by regulating Th1/Th2/Th17 imbalance.