Oliveira Thais M, Sakai Vivien T, Machado Maria Aparecida A M, Dionísio Thiago J, Cestari Tania Mary, Taga Rumio, Amaral Sandra L, Santos Carlos F
Department of Pediatric Dentistry, Orthodontics and Community Health, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
J Periodontol. 2008 Jun;79(6):1062-9. doi: 10.1902/jop.2008.070411.
Vascular endothelial growth factor (VEGF) is a macromolecule of importance in inflammation that has been implicated in periodontitis. The aims of this study were to investigate VEGF expression during the progression of periodontal disease and to evaluate the effect of a preferential cyclooxygenase (COX)-2 inhibitor meloxicam on VEGF expression and alveolar bone loss in experimentally induced periodontitis.
A total of 120 Wistar rats were randomly separated into groups 1 (control) and 2 (meloxicam, 3 mg/kg/day, intraperitoneally, for 3, 7, 14, or 30 days). Silk ligatures were placed at the gingival margin level of the lower right first molar of all rats. VEGF expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemical (IHC) analyses. The hemiarcades were processed for histopathologic analysis. RT-PCR and WB results were submitted to analysis of variance, the Tukey test, and Pearson correlation analysis (P <0.05).
A reduction in alveolar bone resorption was observed in the meloxicam-treated group compared to the control group at all periods studied. There was a positive correlation between COX-2 mRNA and VEGF mRNA in the gingival tissues and periodontal disease (R = 0.80; P = 0.026). Meloxicam significantly reduced the increased mRNA VEGF expression in diseased tissues after 14 days of treatment (P = 0.023). Some alterations in VEGF receptor 1 mRNA expression were observed, but these were not statistically significant. VEGF protein expression in WB experiments was significantly higher in diseased sites compared to healthy sites (P <0.05). After 14 days of treatment with meloxicam, an important decrease in VEGF protein expression was detected in diseased tissues (P = 0.08). Qualitative IHC analysis revealed that VEGF protein expression was higher in diseased tissues and decreased in tissues from rats treated with meloxicam.
The present data suggest an important role for VEGF in the progression of periodontal disease. Systemic therapy with meloxicam can modify the progression of experimentally induced periodontitis in rats by reducing VEGF expression and alveolar bone loss.
血管内皮生长因子（VEGF）是炎症中一种重要的大分子，与牙周炎有关。本研究的目的是调查牙周疾病进展过程中VEGF的表达情况，并评估选择性环氧化酶（COX）-2抑制剂美洛昔康对实验性诱导的牙周炎中VEGF表达和牙槽骨吸收的影响。
总共120只Wistar大鼠被随机分为1组（对照组）和2组（美洛昔康组，腹腔注射3mg/kg/天，持续3、7、14或30天）。在所有大鼠右下第一磨牙的牙龈边缘水平放置丝线结扎。通过逆转录-聚合酶链反应（RT-PCR）、蛋白质免疫印迹（WB）和免疫组织化学（IHC）分析评估VEGF表达。对半侧牙弓进行组织病理学分析。RT-PCR和WB结果进行方差分析、Tukey检验和Pearson相关分析（P<0.05）。
在所有研究时期，与对照组相比，美洛昔康治疗组的牙槽骨吸收减少。牙龈组织中COX-2mRNA与VEGFmRNA以及牙周疾病之间存在正相关（R=0.80；P=0.026）。治疗14天后，美洛昔康显著降低了患病组织中VEGFmRNA表达的增加（P=0.023）。观察到VEGF受体1mRNA表达有一些变化，但这些变化无统计学意义。在WB实验中，患病部位的VEGF蛋白表达明显高于健康部位（P<0.05）。美洛昔康治疗14天后，在患病组织中检测到VEGF蛋白表达显著降低（P=0.08）。定性IHC分析显示，患病组织中VEGF蛋白表达较高，而在美洛昔康治疗的大鼠组织中降低。
目前的数据表明VEGF在牙周疾病进展中起重要作用。美洛昔康全身治疗可通过降低VEGF表达和牙槽骨吸收来改变实验性诱导的大鼠牙周炎的进展。
