Cytological and pharmacological studies on the pathogenesis of nifedipine-associated gingival hyperplasia

1. 我们选择了就诊于东京医科齿科大学牙科医院的 12 名对硝苯地平有反应且牙龈增生的牙周炎患者（有效组）和 4 名对硝苯地平有反应但无牙龈增生的牙周炎患者。采用高效液相色谱法检测服用硝苯地平后6小时血清中硝苯地平的浓度。硝苯地平血清浓度与牙龈增生指数有相关性，但相关性不显着。 2．人牙龈成纤维细胞（HGF）取自反应组和牙周健康受试者。我们研究了硝苯地平及其代谢物对应答组 HGF 和牙周健康受试者 HGF 中蛋白聚糖产生的影响。硝苯地平以剂量依赖性方式诱导应答组 HGF 中蛋白多糖的产生。相反，硝苯地平以剂量依赖性方式抑制牙周健康受试者的 HGF 中蛋白多糖的产生。硝苯地平的代谢物也有类似作用。 3．在源自牙周健康牙龈的 HGF 中检查了源自牙龈卟啉单胞菌和伴放线放线菌的脂多糖 (LPS) 对蛋白聚糖产生的影响。 LPS对蛋白多糖的产生没有影响。4．在源自牙周健康牙龈的 HGF 中检查了各种细胞因子（包括 IL-4、IL-13、INF-γ 和 TNFα）对原聚糖产生的影响。 IL-4 和 IL-13 显着增加了蛋白聚糖的总量，但 INF-gamma 却降低了蛋白聚糖的总量。 TNFα增加了培养基中蛋白多糖的产生，但减少了细胞质中的蛋白多糖产生。 IL-4 和 TNFα 或 IL-13 和 TNFα 的组合可协同上调培养基中的蛋白多糖产量，并略微增强细胞质中的蛋白多糖产量。

1. We selected 12 periodontitis patients with gingival hyperplasia in response to nifedipine (responder group) and 4 periodontitis patients with no gingival hyperplasia in response to nifedipine who visited Dental hospital at Tokyo Medical and Dental University. The concentration of nifedipine in serum 6 h after intake of nifedipine was examined using high performance liquid chromatography. The concentration of nifedipine in serum tended to be associated with gingival hyperplasia index, but the association was not significant.2. Human gingival fibroblasts (HGF) were obtained from responder group and periodontally healthy subjects. We examined the effect of nifedipine and its metabolite on proteoglycan production in HGF from responder group and in HGF from periodontally healthy subjects. Nifedipine induced proteoglycan production in a dose-dependent fashion in HGF from responder group. In contrast, nifedipine depressed proteoglycan production in a dose-dependent manner in HGF from periodontally healthy subjects. A metabolite of nifedipine had similar effects.3. The effect of lipopolysaccharides (LPS) derived from P. gingivalis and A. actinomycetemcomitans on proteoglycan production was examined in HGF derived from periodontally healthy gingiva. The LPS had no effect on proteoglycan production.4. The effect of various cytokines including IL-4, IL-13, INF-gamma and TNFalpha on protoglycan production was examined in HGF derived from periodontally healthy gingiva. IL-4 and IL-13 significantly enhanced total amounts of proteoglycans, but INF-gamma decreased them. TNFalpha increased proteoglycan production in the culture medium, but decreased it in the cytosol. Combination of IL-4 and TNFalpha or IL-13 and TNFalpha synergistically upregulated proteoglycan production in the culture medium and slightly enhanced it in the cytosol.