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肿瘤坏死因子-α阻断对肥胖糖尿病Zucker大鼠实验性牙周炎和2型糖尿病的影响。

Effects of TNF-α blocking on experimental periodontitis and type 2 diabetes in obese diabetic Zucker rats.

作者信息

Grauballe Morten Bay, Østergaard Jakob Appel, Schou Søren, Flyvbjerg Allan, Holmstrup Palle

机构信息

Section for Periodontology, Faculty of Health, Aarhus University, Aarhus, Denmark.

The Medical Research Laboratories, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.

出版信息

J Clin Periodontol. 2015 Sep;42(9):807-816. doi: 10.1111/jcpe.12442. Epub 2015 Sep 28.

Abstract

OBJECTIVE

Tumour necrosis factor α (TNF-α) is considered a key signalling modulator in the pathogenesis of both periodontitis (PD) and type 2 diabetes mellitus (DM2). This study aims at elucidating the effect of TNF-α blocking on the interplay between PD and DM2.

METHODS

Obese diabetic Zucker rats and their lean littermates were divided into five treatment groups with or without periodontitis. Anti-TNF-α treatment was provided with Etanercept injections. Diabetic state was evaluated by oral glucose tolerance test, the homeostatic model assessment, free fatty acids and blood glucose. Systemic inflammation was assessed by measurement of interleukin (IL)-1β, IL-6 and TNF-α in plasma. Kidney complications were evaluated by real-time rtPCR, creatinine clearance rate, urinary albumin excretion and increase in weight. PD was evaluated by registration of alveolar bone level.

RESULTS

After 4 weeks the diabetic state was modified by Etanercept treatment with lower insulin levels and lower homeostatic model assessment. Furthermore, while kidney complications were reduced by Etanercept treatment, PD had no effect. PD was influenced by diabetic state, but the impact was attenuated by Etanercept treatment.

CONCLUSION

In this study anti-TNF-α treatment improved glucose tolerance and compensated for the increased periodontal disease in obese diabetic Zucker. PD did not influence diabetic parameters assessed including complications of the rats kidneys.

摘要

目的

肿瘤坏死因子α(TNF-α)被认为是牙周炎(PD)和2型糖尿病(DM2)发病机制中的关键信号调节因子。本研究旨在阐明TNF-α阻断对PD和DM2相互作用的影响。

方法

将肥胖糖尿病Zucker大鼠及其瘦同胞分为五组,分别进行有无牙周炎的处理。通过注射依那西普进行抗TNF-α治疗。通过口服葡萄糖耐量试验、稳态模型评估、游离脂肪酸和血糖评估糖尿病状态。通过测量血浆中的白细胞介素(IL)-1β、IL-6和TNF-α评估全身炎症。通过实时rtPCR、肌酐清除率、尿白蛋白排泄和体重增加评估肾脏并发症。通过记录牙槽骨水平评估PD。

结果

4周后,依那西普治疗改善了糖尿病状态,胰岛素水平降低,稳态模型评估值降低。此外,依那西普治疗减少了肾脏并发症,但对PD没有影响。PD受糖尿病状态影响,但依那西普治疗减弱了这种影响。

结论

在本研究中,抗TNF-α治疗改善了肥胖糖尿病Zucker大鼠的葡萄糖耐量,并弥补了牙周疾病的增加。PD未影响所评估的糖尿病参数,包括大鼠肾脏的并发症。

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