Enhanced Oxidative Damage and Nrf2 Downregulation Contribute to the Aggravation of Periodontitis by Diabetes Mellitus
Enhanced Oxidative Damage and Nrf2 Downregulation Contribute to the Aggravation of Periodontitis by Diabetes Mellitus
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氧化损伤增强和 Nrf2 下调导致糖尿病引起的牙周炎加重
DOI：
10.1155/2018/9421019
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Huang, Shengbin
中科院分区：
文献类型：
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作者：
Li, Xumin;Sun, Xiaoyu;Huang, Shengbin
糖尿病是牙周炎的一个公认的危险因素。本研究的目的是阐明氧化应激和核因子红细胞2相关因子2 （Nrf2）是否参与糖尿病牙周炎的加重。为此，我们将Wistar大鼠分为对照组、牙周炎组、糖尿病组和糖尿病牙周炎组。链脲佐菌素诱导糖尿病2周后结扎引起牙周炎。两周后，收集牙周组织和血液，通过体视显微镜、免疫组织化学和实时聚合酶链反应进行分析。结扎术后糖尿病大鼠骨质流失和牙周细胞凋亡较正常大鼠严重（p < 0.05）。与对照组相比，牙周炎显著增加了局部氧化损伤（3-硝基酪氨酸、4-羟基-2-壬烯醛和8-羟基脱氧鸟苷表达升高），而糖尿病显著增加了全身氧化损伤并抑制了抗氧化能力（丙二醛表达升高，超氧化物歧化酶活性降低）（p < 0.05）。牙周炎和糖尿病同时加重了局部和全身氧化损伤（p < 0.05）；这一发现与糖尿病牙周炎患者更严重的牙周破坏密切相关。糖尿病牙周炎患者Nrf2基因及蛋白表达均显著下调（p < 0.05）。多元回归分析表明，Nrf2表达降低与糖尿病牙周炎患者牙周破坏和氧化损伤加重密切相关。我们得出结论，局部和全身氧化损伤的增强以及Nrf2的下调有助于糖尿病牙周炎的发生和进展。
Diabetes mellitus is a well-recognized risk factor for periodontitis. The goal of the present study was to elucidate whether oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) participate in the aggravation of periodontitis by diabetes. For this purpose, we assigned Wistar rats to control, periodontitis, diabetes, and diabetic periodontitis groups. Two weeks after induction of diabetes by streptozotocin, periodontitis was induced by ligation. Two weeks later, periodontal tissues and blood were harvested and analyzed by stereomicroscopy, immunohistochemistry, and real-time polymerase chain reaction. We found that ligation induced more severe bone loss and periodontal cell apoptosis in diabetic rats than in normal rats (p < 0.05). Compared with the control group, periodontitis significantly enhanced local oxidative damage (elevated expression of 3-nitrotyrosine, 4-hydroxy-2-nonenal, and 8-hydroxy-deoxyguanosine), whereas diabetes significantly increased systemic oxidative damage and suppressed antioxidant capacity (increased malondialdehyde expression and decreased superoxide dismutase activity) (p < 0.05). Simultaneous periodontitis and diabetes synergistically aggravated both local and systemic oxidative damage (p < 0.05); this finding was strongly correlated with the more severe periodontal destruction in diabetic periodontitis. Furthermore, gene and protein expression of Nrf2 was significantly downregulated in diabetic periodontitis (p < 0.05). Multiple regression analysis indicated that the reduced Nrf2 expression was strongly correlated with the aggravated periodontal destruction and oxidative damage in diabetic periodontitis. We conclude that enhanced local and systemic oxidative damage and Nrf2 downregulation contribute to the development and progression of diabetic periodontitis.