Fibroblastic growth and responses of fibroblast to calcium in druginduced gingival overgrowth

药物诱导的牙龈过度生长中成纤维细胞的生长和成纤维细胞对钙的反应

• 批准号: 10671933
• 负责人: MORISAKI Ichijiro
• 金额: $ 1.92万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671933/
• 关键词: gingival overgrowth; calcium blocker; nifedipine; diltiazem; cyclosporin; シクロオスポリン; 線維芽細胞

1. In vivo experiment : Fifteen-day-old Fischer rats were fed powdered diet containing cyclosporin A (50-300μg/g), nifedipine (200-600μg/g) or diltiazem (600-6000μg/g) for 40 days. Other two rat groups were fed the diet containing CsA and either of the Ca blocker concurrently. CsA induced the most severe GO, followed by nifedipine and diltiazem in order. Combined drug treatment induced more severe GO in the rats than those treated with single drug, and that effect appeared synergistically.2. Clinical observation : Periodontal conditions of patient taking amlodipine were monitored for more than 6 months. Suspension of the drug improved the patient's periodontal conditions, however, recurrent GO was observed by restarting the drug.3. In vitro experiment : Both growth and apoptosis of the cultured human gingival fibroblasts were suppressed by the nifedipine, however, the cell growth was more affected than the apoptosis by the drug. Nifedipine also inhibited the induced-NO synthetase in LPS stimulated macrophages, suggesting that the drug inhibits the fibroblast death especially in the inflamed gingival tissue.

1.体内实验：15日龄Fischer大鼠分别饲喂含环孢菌素A（50-300μg/g）、硝苯地平（200-600μg/g）或地尔硫卓（600-6000μg/g）的粉状饲料40天。另外两组大鼠同时喂食含CsA和任一种Ca受体阻滞剂的饲料。CsA诱发的GO最严重，其次是硝苯地平和地尔硫卓。结论1.联合用药较单一用药诱发大鼠GO加重，且具有协同作用.临床观察：监测患者服药后6个月以上的牙周情况。停药后患者牙周状况得到改善，但再次用药后GO复发。体外实验：硝苯地平对体外培养的人牙龈成纤维细胞的生长和凋亡均有抑制作用，但对细胞生长的影响大于对凋亡的影响。硝苯地平还抑制LPS刺激的巨噬细胞中诱导的NO合成酶，这表明药物抑制成纤维细胞的死亡，特别是在发炎的牙龈组织中。

项目成果

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Miyawaki、Yasuko 等人：“大鼠周乳头发育和再生中的 Calbindine D28K 样免疫反应性”细胞组织研究。

Watanabe,kazufumi et al: "Bilirubin pigmentation of human teeth caused by hyperbilirubinemia" Jounal of Oral Patbology and Medicine. (in press).

Watanabe，kazufumi 等：“高胆红素血症引起的人类牙齿胆红素色素沉着”口腔病理学和医学杂志。

Amano Atsuo et al.: "Molecular interactions of Porphyromonas gingivalis fimbriae with host proteins: kinetic analyses based on surface plasmon resonance"Infection and Immunity. 67. 2399-2405 (1999)

Amano Atsuo 等人：“牙龈卟啉单胞菌菌毛与宿主蛋白的分子相互作用：基于表面等离子体共振的动力学分析”感染和免疫。

Kataoka Masatoshi et al.: "Cyclosporin A decreases the degradation of type I collagen in rat gingival overgrowth"Journal of Cell Physiology. 182. 351-358 (2000)

Kataoka Masatoshi 等人：“环孢菌素 A 减少大鼠牙龈过度生长中 I 型胶原蛋白的降解”《细胞生理学杂志》。

Morisaki Ichijiro et al.: "Effects of combines oral treatment with cyclosporin A and nifedipine or diltiazem on drug-induced gingival overgrowth in rats"Journal of Periodontology. 71. 437-443 (2000)

Morisaki Ichijiro 等人：“环孢素 A 与硝苯地平或地尔硫卓联合口服治疗对大鼠药物性牙龈过度生长的影响”牙周病学杂志。