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他汀类药物对中老年 2 型糖尿病患者牙龈沟液和唾液细胞因子水平及临床牙周参数的影响。

Effects of statins on cytokines levels in gingival crevicular fluid and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus.

机构信息

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Shenzhen Center for Chronic Disease Control, Shenzhen, China.

出版信息

PLoS One. 2021 Jan 8;16(1):e0244806. doi: 10.1371/journal.pone.0244806. eCollection 2021.

Abstract

OBJECTIVE

To analyze the effect of statins on cytokines levels in gingival crevicular fluid (GCF) and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus (T2DM).

METHODS

Systemically healthy controls (C group, n = 62), T2DM patients not taking statins (D group, n = 57) and T2DM patients taking statins (S group, n = 24) were recruited. In each group, subjects (40-85 years) were subclassified into the h (periodontal health)group, the g (gingivitis)group or the p (periodontitis) group according to different periodontal conditions. 17 cytokines in gingival crevicular fluid (GCF) and saliva samples of each subject were measured utilizing the Luminex technology kit. Further, HbA1c (glycated hemoglobin), FPG (fasting plasma glucose), PD (probing depth), CAL (clinical attachment level), BOP (bleeding on probing), GI (gingival index) and PI (periodontal index) were recorded. Data distribution was tested through the Shapiro-Wilk test, upon which the Kruskal-Wallis test was applied followed by Mann-Whitney U test and Bonferroni's correction.

RESULTS

Levels of IFN-γ, IL-5, IL-10 and IL-13 in the saliva of the Dh group were significantly lower than those in the Ch group, while factor IL-4 was higher (p<0.05). Levels of MIP-3α, IL-7 and IL-2 in GCF of the Dh group were considerably higher than those in the Ch group (p<0.05), while that of IL-23 was considerably lower. Compared with the Cg group, levels of IFN-γ, IL-4, IL-5, IL-6, IL-10 and IL-13 were significantly lower in the saliva of the Dg group (p<0.05). Lower levels of IFN-γ, IL-5 and IL-10 were detected in the Sg group than those in the Cg group (p<0.05). At the same time, levels of IL-1β, IL-6, IL-7, IL-13, IL-17, IL-21 and MIP-3α in the gingival crevicular fluid of the Sg group were lower in comparison with the Dg group. In addition, lower levels of IL-4 and higher levels of IL-7 in GCF were identified in the Dg group than those in the Cg group, while in the Sg group, lower levels of IL-4, MIP-1αand MIP-3αwere observed than those in the Cg group (p<0.05). Lower levels of IFN-γ, IL-6, IL-10, IL-13 and I-TAC were found in the Sp group compared with those in the Cp group. The IFN-γ, IL-6 and IL-10 levels were lower in the Dp group than those in the Cp group (p<0.05). Meanwhile, in the Sp group, lower levels of pro-inflammatory factors IFN-γ, IL-1β, IL-2, IL-6, IL-7, IL-21 and TNF-α, in addition to higher levels of anti-inflammatory factors IL-4 and IL-5 in gingival crevicular fluid, were identified than those in the Dp group. Higher levels of IFN-γ,IL-1β,IL-2,IL-7,IL-21 and TNF-α and a lower level of IL-5 in the Dp group were identified than those in the Cp group (p<0.05). Moreover, statins were able to substantially reduce PD in T2DM patients with periodontitis, indicating an obvious influence on the levels of cytokines secreted by Th1 cells, Th2 cells and Th17 cells, as revealed by PCA (principal component analysis).

CONCLUSION

Statins are associated with reduced PD and cytokines levels in the GCF and saliva of T2DM patients with periodontitis.

摘要

目的

分析他汀类药物对 2 型糖尿病(T2DM)中老年人龈沟液(GCF)和唾液中细胞因子水平及临床牙周参数的影响。

方法

选择 62 例系统性健康对照(C 组)、57 例未服用他汀类药物的 T2DM 患者(D 组)和 24 例服用他汀类药物的 T2DM 患者(S 组)。根据不同的牙周状况,将每组(40-85 岁)受试者分为 h(牙周健康)组、g(牙龈炎)组或 p(牙周炎)组。采用 Luminex 技术试剂盒测量每位受试者的龈沟液(GCF)和唾液中的 17 种细胞因子。同时记录 HbA1c(糖化血红蛋白)、FPG(空腹血糖)、PD(探诊深度)、CAL(临床附着水平)、BOP(探诊出血)、GI(牙龈指数)和 PI(牙周指数)。通过 Shapiro-Wilk 检验检验数据分布,然后应用 Kruskal-Wallis 检验,随后进行 Mann-Whitney U 检验和 Bonferroni 校正。

结果

Dh 组唾液中 IFN-γ、IL-5、IL-10 和 IL-13 水平明显低于 Ch 组,而因子 IL-4 较高(p<0.05)。Dh 组 GCF 中 MIP-3α、IL-7 和 IL-2 水平明显高于 Ch 组(p<0.05),而 IL-23 水平明显较低。与 Cg 组相比,Dg 组唾液中 IFN-γ、IL-4、IL-5、IL-6、IL-10 和 IL-13 水平明显降低(p<0.05)。Sg 组与 Cg 组相比,唾液中 IFN-γ、IL-5 和 IL-10 水平较低(p<0.05)。同时,Sg 组龈沟液中 IL-1β、IL-6、IL-7、IL-13、IL-17、IL-21 和 MIP-3α 水平低于 Dg 组。此外,Dg 组 GCF 中 IL-4 水平较高,IL-7 水平较低,而 Sg 组 GCF 中 IL-4、MIP-1α和 MIP-3α 水平较低(p<0.05)。与 Cg 组相比,Sp 组 IL-4、IL-6、IL-10、IL-13 和 I-TAC 水平较低。与 Cp 组相比,Dp 组 IFN-γ、IL-6 和 IL-10 水平较低(p<0.05)。同时,Sp 组龈沟液中促炎因子 IFN-γ、IL-1β、IL-2、IL-6、IL-7、IL-21 和 TNF-α 水平较低,抗炎因子 IL-4 和 IL-5 水平较高,与 Dp 组相比。与 Cp 组相比,Dp 组 IFN-γ、IL-1β、IL-2、IL-7、IL-21 和 TNF-α 水平较高,IL-5 水平较低(p<0.05)。此外,他汀类药物可显著降低 T2DM 伴牙周炎患者的 PD,通过 PCA(主成分分析)显示其对 Th1 细胞、Th2 细胞和 Th17 细胞分泌的细胞因子水平有明显影响。

结论

他汀类药物与 T2DM 伴牙周炎患者龈沟液和唾液中 PD 及细胞因子水平降低有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/850f/7793287/32551fed7c63/pone.0244806.g001.jpg

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