Influence (Gingival Hyperplasia) of Nifedipine in Oral Region

据报道，苯妥英钠，环孢素A，钙通道阻滞剂引起牙龈增生。特别是，已经报道了一些关于苯妥英的研究。有趣的是，这些化合物均具有一定的钙阻滞作用，但未见钙阻滞作用与牙龈增生关系的研究报道。近年来，钙通道阻滞剂被广泛应用于心血管系统疾病的治疗，但其不良反应常伴有牙龈增生。在钙通道阻滞剂中，硝苯地平引起的频率最高，出现率为6 - 30%。常见的组织病理学观察结果是成纤维细胞数量增加，纤维结缔组织（胶原纤维）增加。炎性变化（如细胞浸润和毛细血管扩张）和心率钉不规则延长。为阐明硝苯地平治疗牙龈增生的机制，本研究采用大鼠离体实验，观察硝苯地平对牙龈增生的影响。 ...更多信息 本实验通过比较硝苯地平反应患者（NIFr）和非反应患者（NIFn）的牙龈成纤维细胞，研究了钙通道阻滞剂对这两种细胞系的影响，结果表明，在钙通道阻滞剂存在下，NIFr的细胞增殖率、DNA合成和胶原合成均高于非反应患者。细胞内钙离子的瞬时快速变化是细胞增殖或分化的重要启动因素之一。因此，研究了化学介质对细胞内钙（[Ca^2+]i）反应的影响，因为在大多数情况下炎症伴随牙龈增生。结果表明，缓激肽、凝血酶、PGE_28、PGF_3、PDGF对NIF_n来源的牙龈成纤维细胞[Ca^2]i反应有显著影响<2alpha>，而组胺和蛙皮素对NIF_r来源的牙龈成纤维细胞[Ca^2]i反应有显著影响。因此，组胺在牙龈增生中可能起着更重要的作用。缓激肽对NIFn来源的牙龈成纤维细胞[Ca^&lt;2+&gt;]i反应的影响最大。缓激肽引起的[Ca^&lt;2+&gt;]i反应具有温度依赖性，在37 ℃时达到最高，缓激肽B_2拮抗剂可抑制这种反应。少

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