Gyurkovics Milán, Lohinai Zsolt, Gyorfi Adrienne, Iványi Iván, Süveges Ibolya, Kónya Mária, Bodor Csaba, Székely Andrea D, Dinya Elek, Fazekas Arpád, Rosivall László
Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary.
J Periodontol. 2009 Sep;80(9):1518-23. doi: 10.1902/jop.2009.080651.
Endothelial cell proliferation, angiogenesis, and increased vascular permeability are among the effects of vascular endothelial growth factor (VEGF) in various organs. However, the effects of VEGF on gingival hemodynamics, especially on venules, have not been thoroughly investigated. This study investigated the acute circulatory effects of VEGF on rat gingival venules.
Fifty-six anesthetized rats were divided into five study groups; each rat received 10 microl of experimental solution dripped onto the lower interincisal gingiva. The groups included: 1) saline control (after the experiment, gingiva was excised for VEGF receptor 2 [VEGFR2] immunohistochemistry); 2) VEGF (0.1, 1, 10, or 50 microg/ml); 3) VEGF2 receptor antagonist 5-((7-benzyloxyquinazolin-4-yl)amino)-4-fluoro-2-methyl-phenol-hydrochloride (ZM323881; 20 microg/ml); 4) ZM323881 (20 microg/ml) followed by VEGF application (50 microg/ml after 15 minutes); and 5) VEGF (10 microg/ml), these rats were premedicated with nitric oxide (NO) synthase blocker (N(G)-nitro-L-arginine-methyl-ester [L-NAME]; 1 mg/ml in drinking water) for 1 week before the experiment. Changes in gingival superficial venule diameter were measured by vital microscopy prior to and 1, 5, 15, 30, and 60 minutes after the administration of the experimental solutions.
VEGF dose-dependently increased the venular diameter compared to saline. ZM323881 alone did not cause any alteration. Premedication with ZM323881 or L-NAME decreased the dilatory effects of VEGF. VEGFR2 immunohistochemical labeling was observed in the wall of the venules.
There is no remarkable VEGF production under physiologic circumstances in rat gingiva, but VEGF is able to increase gingival blood flow through the activation of VEGF2 receptors. Furthermore, NO release may contribute to VEGF's vasodilatory effect.
血管内皮生长因子（VEGF）在各器官中的作用包括内皮细胞增殖、血管生成以及血管通透性增加。然而，VEGF对牙龈血流动力学的影响，尤其是对小静脉的影响，尚未得到充分研究。本研究调查了VEGF对大鼠牙龈小静脉的急性循环影响。
将56只麻醉大鼠分为五个研究组；每只大鼠在下颌切牙间牙龈滴注10微升实验溶液。这些组包括：1）生理盐水对照组（实验后，切除牙龈进行VEGF受体2 [VEGFR2]免疫组织化学检测）；2）VEGF（0.1、1、10或50微克/毫升）；3）VEGF2受体拮抗剂5 - （（7 - 苄氧基喹唑啉 - 4 - 基）氨基） - 4 - 氟 - 2 - 甲基苯酚盐酸盐（ZM323881；20微克/毫升）；4）ZM323881（20微克/毫升），随后应用VEGF（15分钟后为50微克/毫升）；5）VEGF（10微克/毫升），这些大鼠在实验前1周用一氧化氮（NO）合酶阻滞剂（N（G） - 硝基 - L - 精氨酸甲酯[L - NAME]；饮用水中1毫克/毫升）进行预处理。在给予实验溶液前以及给药后1、5、15、30和60分钟，通过活体显微镜测量牙龈浅表小静脉直径的变化。
与生理盐水相比，VEGF剂量依赖性地增加了小静脉直径。单独使用ZM323881未引起任何改变。用ZM323881或L - NAME预处理可降低VEGF的扩张作用。在小静脉壁观察到VEGFR2免疫组织化学标记。
在大鼠牙龈的生理情况下，没有显著的VEGF产生，但VEGF能够通过激活VEGF2受体增加牙龈血流量。此外，NO释放可能有助于VEGF的血管舒张作用。
