Effects of periodontitis on aortic insulin resistance in an obese rat model

Effects of periodontitis on aortic insulin resistance in an obese rat model
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DOI:
10.1038/labinvest.2009.141
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发表时间:
2010-03-01
影响因子:
5
通讯作者:
Morita, Manabu
Morita, Manabu
中科院分区:
医学2区
文献类型:
--
作者:
Ekuni, Daisuke;Tomofuji, Takaaki;Morita, Manabu

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肥胖及其相关风险因素(如胰岛素抵抗和炎症)的结合导致动脉粥样硬化的发展。然而,牙周炎对肥胖者动脉粥样硬化的影响尚不清楚。本研究的目的是通过评估主动脉胰岛素抵抗来研究结扎诱导的Zucker肥胖大鼠牙周炎对动脉粥样硬化起始的影响。Zucker脂肪大鼠(n = 24)分为两组。在牙周炎组中,牙周炎结扎诱导4周,而对照组保持不结扎。实验4周后,取降主动脉行脂质沉积、免疫组化及基因表达检测。还测量了血清C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)和胰岛素水平。牙周炎组大鼠主动脉脂质沉积明显增加,而对照组无明显变化。牙周炎组细胞因子信号转导抑制因子3、血管细胞粘附分子1、活性氧、硝基酪氨酸和内皮素-1的表达较对照组明显增强。在牙周炎组中观察到磷脂酰肌醇3-激酶(Pi 3 k)催化β-多肽(Pi 3 kcb)、Pi 3 kp 85和胰岛素受体底物1和2的水平显著降低。牙周炎组血清CRP和TNF-α水平显著升高。在胰岛素刺激的条件下,牙周炎组的主动脉改变Akt磷酸化。肥胖性牙周炎可诱导动脉粥样硬化的早期阶段,并干扰主动脉胰岛素信号传导。
The combination of obesity and its associated risk factors, such as insulin resistance and inflammation, results in the development of atherosclerosis. However, the effects of periodontitis on atherosclerosis in an obese body remain unclear. The aim of the study was to investigate the effects of ligature-induced periodontitis in Zucker fatty rats on initiation of atherosclerosis by evaluating aortic insulin resistance. Zucker fatty rats (n = 24) were divided into two groups. In the periodontitis group, periodontitis was ligature-induced for 4 weeks, whereas the control group was left unligated. After the 4-week experimental period, descending aorta was used for measuring the levels of lipid deposits, immunohistochemical analysis, and evaluation of gene expression. Levels of serum C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and insulin were also measured. Rats in the periodontitis group had significantly enhanced lipid deposits in the aorta, but not in the control group. Expression of suppressor of cytokine signaling 3, vascular cell adhesion molecule 1, reactive oxygen species, nitrotyrosine, and endothelin-1 in the periodontitis group was more intense than that in the control group. Significantly decreased levels of phosphatidylinositol 3-kinase (Pi3k) catalytic beta-polypeptide (Pi3kcb), Pi3kp85, and insulin receptor substrate 1 and 2 were observed in the periodontitis group. Levels of serum CRP and TNF-alpha were significantly increased in the periodontitis group. Under insulin-stimulated conditions, aorta in the periodontitis group altered the Akt phosphorylation. Periodontitis in obesity induced the initial stage of atherosclerosis and disturbed aortic insulin signaling.