Infliximab attenuates inflammatory osteolysis in a model of periodontitis in Wistar rats
Infliximab attenuates inflammatory osteolysis in a model of periodontitis in Wistar rats
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DOI：
10.1177/1535370213520114
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发表时间：
2014-04-01
影响因子：
3.2
通讯作者：
Oria, Reinaldo B.
中科院分区：
文献类型：
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作者：
Goncalves, Davi C.;Evangelista, Rakel C.;Oria, Reinaldo B.
牙周炎是一种与成人牙齿脱落有关的慢性炎症性疾病。英夫利昔单抗是一种针对tnf - α的嵌合单克隆抗体，用于治疗全身性炎性疾病。本研究旨在探讨英夫利昔单抗在实验性牙周病（EPD）中的作用。Wistar大鼠左上第二磨牙经3.0尼龙线诱导EPD。动物在牙周炎诱导前30分钟静脉注射英夫利昔单抗（1、5、7和10 mg/kg）或生理盐水，并随访至第11天处死。第三天对一部分大鼠实施安乐死，分析牙龈髓过氧化物酶（MPO）和血液MPO粒细胞指数。此外，我们使用共聚焦显微镜分析了骨质流失指数（BLI）、牙周组织病理学评分和牙周胶原网络。免疫组化法检测上颌组织金属蛋白酶-1/-8、RANK、RANK- l、骨保护素；ELISA法检测牙龈MPO、IL-1 β、tnf - α。EPD引起白细胞增多，BLI和牙龈促炎细胞因子及细胞浸润明显增加，组织病理学评分加重，牙周胶原蛋白紊乱。与挑战生理盐水组相比，英夫利昔单抗（5mg /kg）降低了粒细胞血细胞计数、牙龈IL-1 β、tnf - α和MPO水平，降低了MMP-1/-8、RANK和RANK- l骨免疫标记，并具有更好的牙周组织病理学评分和胶原网络。我们得出结论，英夫利昔单抗对牙周炎损伤的Wistar大鼠具有显著的抗炎和骨保护作用。
Periodontitis is a chronic inflammatory disease related to tooth loss in adults. Infliximab is a chimeric monoclonal antibody against TNF-alpha and is prescribed for the treatment of systemic inflammatory diseases. This study aimed to investigate the role of infliximab on experimental periodontal disease (EPD). EPD was induced by passing a 3.0 nylon thread around the upper left second molar in Wistar rats. Animals were either treated with intravenous infliximab (1, 5, 7, and 10 mg/kg) or saline solution 30 min before the periodontitis induction and were followed until they were sacrificed on the 11th day. A subset of rats was euthanized on the third day for analysis of gingival myeloperoxidase (MPO) and the blood MPO granulocyte index. In addition, we analyzed the bone loss index (BLI), the periodontal histopathological score, and the periodontal collagen network using confocal microscopy. We also analyzed metalloproteinase-1/-8, RANK, RANK-L, and osteoprotegerin in maxillary tissue by immunohistochemistry Gingival MPO, IL-1 beta, TNF-alpha were measured by ELISA. EPD caused leukocytosis, significant increases in BLI and gingival pro-inflammatory cytokines and cell infiltrates, with worse histopathological scores and periodontal collagen derangement. Infliximab (5 mg/kg) reduced granulocyte blood counts, gingival IL-1 beta, TNF-alpha, and MPO levels, diminished MMP-1/-8, RANK, and RANK-L bone immunolabeling with better periodontal histopathological scores and collagen network in comparison with the challenged saline group. We concluded that infliximab had significant anti-inflammatory and bone-protective effects in Wistar rats challenged by periodontitis.