Influence (Gingival Hyperplasia) of Nifedipine in Oral Region

硝苯地平对口腔的影响（牙龈增生）

• 批准号: 04671133
• 负责人: FUJII Akira
• 金额: $ 0.45万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671133/
• 关键词: Gingival hyperplasia; Nifedipine; Gingival fibroblasts; Tissue culture; Intracellular calcium resoinse; Bradykinin; 細胞増殖; DNA合成能; カルシウム拮抗薬; フェニトン; ヒスタミン; カルシウム拮抗剤; 線維芽細胞; コラーゲン合成能; カルシウム取り込み; 細胞内カルシウム濃度

It has been reported that phenytoin, cyclosporin A, and calcium channel blockers caused gingival hyperplasia. Especially, a number of studies has been reported on phenytoin. The interesting point is that all of these compounds possess somewhat calcium blockin effect, but no report exists on the study between calcium blocking effect and gingival hyperplasia. In recent years, calcium channel blockers have been used extensively for the treatment of disease in cardiovascular system, accompanied with gingival hyperplasia as their untoward effects. Among of the calcium channel blockers, nifedipine caused it most frequently with appearance rate of 6 to 30%. The common histopathological observations are increased number of fibroblasts, increased fibrous connective tissue (collagen fiber). inflammatory changes (such as cell infiltration and dilatation of capillaries), and irregular elongation of rate pegs. In order to clarify the mechanism of gingival hyperplasia by nifedipine, the present inve … More stigation was undertaken to study the effect of calcium channel blockers ongingival fibroblasts derived from nifedipine responder (nifediline reactive patients ; NIFr) and non-responder (nifedipinenon-reactive patients ; NIFn) by comparing these two cell lines.The results show that NIFr gave higher cell proliferation rate, DNA synthesis, and collagen synhesis in the presence of calcium channel blockers. One of the important factor for the initiation of cell proliferation or cell differenciation is the transient and rapid change of intracellular calcium. Thus, the effect of chemical mediators was investigated on intracellular calcium ([Ca^<2+>]i) response, because inflammation was accompanied with gingival hyperplasia in most of the cases. As the result, [Ca^2]i response was greatly affected by bradykinin, thrombin, PGE_28 PGF_<2alpha>, and PDGF in gingival fibroblasts derived fron NIF_n, whereas by histamine and bombesin in ones derived from NIFr. Thus, histamine might play more important role in gingival hyperplasia. Bradykinin gave the greatest effect on [Ca^<2+>]i response in both gingival fibroblasts derived from NIFn. The [Ca^<2+>]i response by bradykinin was temperature dependent and the highest response was obtained at 37ﾟC.This response was inhibited by bradykinin B_2 antagonist. Less

据报道，苯妥英、环孢素A和钙通道阻滞剂可引起牙龈增生。特别是对苯妥英的研究已经有了大量的报道。有趣的是，所有这些化合物都具有一定的钙阻滞作用，但没有关于钙阻滞作用与牙龈增生的研究报道。近年来，钙通道阻滞剂被广泛用于心血管疾病的治疗，其不良反应是伴随牙龈增生。钙通道阻滞剂中以硝苯地平最常见，发生率为6 ~ 30%。常见的组织病理学观察是成纤维细胞数量增加，纤维结缔组织（胶原纤维）增加。炎症改变（如细胞浸润和毛细血管扩张），以及不规则的率钉延伸。为了阐明硝苯地平对牙龈增生的作用机制，本研究通过比较硝苯地平反应性（nifediline reactive patients, NIFr）和硝苯地平无反应性（nifedipinnon -reactive patients, NIFn）两种细胞系，进一步研究钙通道阻滞剂对硝苯地平反应性（nifedipinnon -reactive patients, NIFn）牙龈成纤维细胞的影响。结果表明，在钙通道阻滞剂存在的情况下，NIFr具有更高的细胞增殖率、DNA合成和胶原合成。细胞内钙的瞬时快速变化是细胞增殖或分化发生的重要因素之一。因此，我们研究了化学介质对细胞内钙（[Ca^<2+>]i）反应的影响，因为炎症在大多数情况下伴有牙龈增生。结果表明，NIF_n来源的牙龈成纤维细胞受缓激肽、凝血酶、PGE_28、PGF_<2alpha>和PDGF的影响较大，而NIFr来源的成纤维细胞受组胺和bombesin的影响较大。因此，组胺可能在牙龈增生中发挥更重要的作用。在NIFn衍生的两种牙龈成纤维细胞中，缓激素对[Ca^<2+>]i反应的影响最大。缓激肽对[Ca^<2+>]i的响应与温度有关，在37℃时达到最高响应。缓激肽B_2拮抗剂可抑制这种反应。少