Research on developmental mechanisms of drug-induced gingival overgrowth: experiments in animal and cellular levels

药物引起的牙龈过度生长的发育机制研究：动物和细胞水平的实验

• 批准号: 13672144
• 负责人: MORISAKI Ichijiro
• 金额: $ 1.86万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672144/
• 关键词: phenytoin; cyclosporin; nifedipine; fibroblast; apotosis; ketoconazole; ニクエジピン

1. Human Gingival Fibroblast Experiments: in vitro1) When effects ofnifedipine, a calcium channel btocfcer, on cell proliferation and apoptosis were examined in human gingival fibroblast (HGF) cultures, both of these were suppressed by the drug in a dose dependent manner2) Nifedipine inhibited lipopolysaccharide (LPS)induced nitric oxide (NO) production and apoptosis of macrophage like cells (RAW264). Furthermore, LPSinduced NO synthetase (iNOS) production was also inhibited by adding nifedipine to the RAW 264 ceil cultures3) LPS stimulation induced the apoptosis ofHGF cultured with RAW264, however, this apoptosis was suppressed by the addition of nifedipine to the culture4) Phenytoin enhanced the mRNA production of matrix metaloproreases (MMPs) and their inhibitors in the HGF culturesThese findings are suggesting that the close relationship exists between the effects ofnifedipine or phenytoin on the proliferation, apoptosis and inflammatory reaction of HGF and the druginduced gingival overgrowth2. Drug Interaction in Gingival Overgrowth in Rats1) To elucidate the effects of drug interaction on gingival overgrowth, rats were treated with nifedipine and/or ketoconazole which affects the nifedipine metabolism. Ketoconazole treatment induced higher blood nifedipine level and more severe gingival overgrowth in rats than those treated with nifedipine only2) When rats were treated with nifedipine and administered grapefruitjuice or bergamot oil concomitantly, an increase in severity of nifedipineinduced gingival overgrowth was found in rats given

1.人牙龈成纤维细胞实验：1)体外观察钙通道阻滞剂硝苯地平对人牙龈成纤维细胞(HGF)增殖和凋亡的影响，并呈剂量依赖性抑制。2)硝苯地平抑制脂多糖(LPS)诱导的一氧化氮(NO)生成和巨噬细胞样细胞(RAW264)的凋亡。此外，在RAW264细胞中加入硝苯地平也能抑制LPS诱导的一氧化氮合酶(INOS)的产生。3)LPS刺激诱导RAW264培养的HGF发生凋亡，而加入硝苯地平则可抑制这种凋亡。4)苯妥英钠能促进HGF中基质金属蛋白酶(MMPs)及其抑制剂的基因表达。1)为了阐明药物相互作用对牙龈过度生长的影响，用硝苯地平和/或酮康唑治疗大鼠，以影响硝苯地平的代谢。与单用硝苯地平的大鼠相比，酮康唑可引起更高的血硝苯地平水平和更严重的牙龈过度生长。2)当给予硝苯地平并同时给予葡萄汁或佛手果油时，发现给予硝苯地平的大鼠牙龈过度生长的严重程度增加。

项目成果

Fukui, N., et al.: "Gingival Overgrowth in Rats Orally Treated with Large Dose of Phenytoin"Dentistry in Japan. 38. 150-154 (2002)

Fukui, N. 等人：“口服大剂量苯妥英治疗大鼠牙龈过度生长”，日本牙科。

Morisaki, Ichijiro et al.: "Amlodipine-inducedugingival overgrowth : periodontal responses to stopping and restarting the drug"Special are in Dentistry. 21. 60-62 (2001)

Morisaki、Ichijiro 等人：“氨氯地平引起的牙龈过度生长：停止和重新开始用药时的牙周反应”，特别是牙科。

Icihijiro,MORJSAKI: "Dental treatment for children with disabilities."Illustrated Clinical Dentistry 4. Dentistry for the child: oral diseases/malociulusion. Ishiyaku Shuppan Co. Ltd. Tokyo (in Japanese). 82-85 (2002)

Icihijiro，MORJSAKI：“残疾儿童的牙科治疗。”临床牙科图解 4。儿童牙科：口腔疾病/畸形。

Kimura, S. et al.: "Periodontopathic Bacterial Infection in Childhood"Journal of Periodontology. 73. 20-26 (2002)

Kimura, S. 等人：“儿童期牙周细菌感染”牙周病学杂志。

Ichiro,NAKAGAWA, Atsuo,AMANO, Ohara,NHMOTO, Ichijiro,MORISAKI, Shigenobu,KllMURA, Shigetada,KAWABATA, Shigeyuki,HAMADA: "Identification of a new variant of fim A gene of Porphyramonas gingivalis and its distribution in adults and disabled population with

Ichiro，NAKAGAWA，Atsuo，AMANO，Ohara，NHMOTO，Ichijiro，MORISAKI，Shigenobu，KllMURA，Shigetada，KAWABATA，Shigeyuki，HAMADA：“牙龈卟啉单胞菌 fim A 基因新变体的鉴定及其在成人和残疾人群体中的分布