慢性牙周炎合并2型糖尿病患者龈沟液Sirtuin-1、Sirtuin-6的变化及临床价值研究

Study on the Changes and Clinical Value of Sirtuin-1 and Sirtuin-6 in Gingival Crevicular Fluid of Chronic Periodontitis Patients with Type 2 Diabetes Mellitus

目的:探讨慢性牙周炎(CP)合并2型糖尿病(T2DM)患者龈沟液沉默信息调节因子-1(Sirtuin-1)、Sirtuin-6的变化和临床价值。方法:选择2020年3月至2023年3月中国人民解放军联勤保障部队第九七〇医院收治的147例CP合并T2DM患者(T2DM组),128例单纯CP患者(CP组)和121例健康体检者(对照组)。根据牙周检查结果将T2DM组患者分为轻度组(n=49)、中度组(n=67)、重度组(n=31)。检测受试者龈沟液中Sirtuin-1、Sirtuin-6水平以及外周血单核细胞核苷酸结合寡聚化结构域样受体热蛋白结构域亚家族成员3(NLRP3)信使核糖核酸(mRNA)、程序性细胞死亡相关斑点样蛋白(ASC)mRNA、半胱氨酸蛋白酶1(Caspase-1)mRNA表达,并评估牙周临床指标。Pearson分析CP合并T2DM患者龈沟液Sirtuin-1、Sirtuin-6水平与牙周临床指标、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达的相关性。受试者工作特征(ROC)曲线分析龈沟液Sirtuin-1、Sirtuin-6诊断CP合并T2DM的价值。结果:T2DM组龈沟液Sirtuin-1、Sirtuin-6水平低于CP组和对照组(P<0.05),出血指数(SBI)、牙周袋探诊深度(PD)、牙龈指数(GI)、菌斑指数(PLI)、附着丧失(AL)、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达高于CP组和对照组(P<0.05)。CP组龈沟液Sirtuin-1、Sirtuin-6水平低于和对照组(P<0.05),GI、SBI、PLI、PD、AL、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达高于对照组(P<0.05)。重度组龈沟液Sirtuin-1、Sirtuin-6水平低于中度组和轻度组(P<0.05),GI、PLI、SBI、AL、PD、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达高于中度组和轻度组(P<0.05)。中度组龈沟液Sirtuin-1、Sirtuin-6水平低于轻度组(P<0.05),GI、PLI、SBI、AL、PD、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达高于轻度组(P<0.05)。CP合并T2DM患者龈沟液Sirtuin-1、Sirtuin-6水平与GI、PLI、SBI、AL、PD、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达均呈负相关(P<0.05)。龈沟液Sirtuin-1、Sirtuin-6诊断CP合并T2DM的曲线下面积(AUC)为0.787、0.806,联合诊断AUC为0.912,高于单独诊断。结论:CP合并T2DM患者龈沟液中Sirtuin-1、Sirtuin-6水平降低,且与牙周组织破坏程度加重、NLRP3炎症小体激活有关。龈沟液Sirtuin-1联合Sirtuin-6在CP合并T2DM诊断中具有较高价值。

Objective:To investigate the changes and clinical value of silent information regulator-1(Sirtuin-1)and Sirtuin-6 in gingival crevicular fluid of chronic periodontitis(CP)patients with type 2 diabetes mellitus(T2DM).Methods:147 CP patients with T2DM(T2DM group),128 patients with simple CP(CP group)and 121 healthy subjects(control group)who were admitted to The 970 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from March 2020 to March 2023 were selected.Patients in T2DM group were divided into mild group(n=49),moderate group(n=67)and severe group(n=31)according to the results of periodontal examination.The levels of Sirtuin-1 and Sirtuin-6 in gingival crevicular fluid and the expression of nucleotide-binding oligomerization domain-like receptor hot protein domain subfamily member 3(NLRP3)messenger ribonucleic acid(mRNA),programmed cell death-associated speck-like protein(ASC)mRNA and cysteine protease 1(Caspase-1)mRNA in peripheral blood mononuclear cells were detected,and the periodontal clinical indexes were evaluated.The correlation between the levels of Sirtuin-1 and Sirtuin-6 in gingival crevicular fluid and periodontal clinical indicators,the expression of NLRP3 mRNA,ASC mRNA and Caspase-1 mRNA in peripher-al blood mononuclear cells in CP patients with T2DM were analyzed by Pearson correlation analysis.The value of Sirtuin-1 and Sirtuin-6 in gingival crevicular fluid in the diagnosis of CP combined with T2DM were analyzed by receiver operating characteristic(ROC)curve.Results:The levels of Sirtuin-1 and Sirtuin-6 in gingival crevicular fluid in T2DM group were lower than those in CP group and control group(P<0.05),the bleeding index(SBI),probing depth(PD),gingival index(GI),plaque index(PLI),attachment loss(AL),NLRP3 mRNA,ASC mRNA and Caspase-1 mRNA expression in peripheral blood mononuclear cells in T2DM group were higher than those in CP group and control group(P<0.05).The levels of Sirtuin-1 and Sirtuin-6 in gingival crevicular fluid in CP group were lower than those in control group(P<0.05),the expressions of GI,SBI,PLI,PD,AL,NLRP3 mRNA,ASC mRNA and Caspase-1 mRNA in peripheral blood mononuclear cells in CP group were higher than those in control group(P<0.05).The levels of Sirtuin-1 and Sirtuin-6 in gingival crevicular fluid in severe group were lower than those in moderate group and mild group(P<0.05).The expression of GI,PLI,SBI,AL,PD,NLRP3 mRNA,ASC mRNA and Caspase-1 mRNA in peripheral blood mononuclear cells in severe group were higher than those in moderate group and mild group(P<0.05).The levels of Sirtuin-1 and Sirtuin-6 in gingival crevicular fluid in moderate group were lower than those in mild group(P<0.05),and the expressions of GI,PLI,SBI,AL,PD,NLRP3 mRNA,ASC mRNA and Caspase-1 mRNA in peripheral blood mononuclear cells were higher than those in mild group(P<0.05).The levels of Sirtuin-1 and Sirtuin-6 in gingival crevicular fluid of CP patients with T2DM were negatively correlated with GI,PLI,SBI,AL,PD,NLRP3 mRNA,ASC mRNA and Caspase-1 mRNA expression in peripheral blood mononuclear cells(P<0.05).The area under the curve(AUC)of Sirtuin-1 and Sirtuin-6 in gingival crevicular fluid for the diagnosis of CP combined with T2DM was 0.787 and 0.806 respectively,and the AUC of combined diagnosis was 0.912,which was higher than that of single diagnosis.Conclusion:The levels of Sirtuin-1 and Sirtuin-6 in gingival crevicular fluid of CP patients with T2DM are decrease,which are relate to the aggravation of periodontal tissue damage and the activation of NLRP3 inflammasome.Sirtuin-1 combine with Sirtuin-6 in gingival crevicular fluid has high value in the diagnosis of CP combine with T2DM.