Kataoka M, Shimizu Y, Kunikiyo K, Asahara Y, Azuma H, Sawa T, Kido J, Nagata T
Department of Periodontology and Endodontology, Tokushima University School of Dentistry, Japan.
J Periodontol. 2001 Aug;72(8):1078-83. doi: 10.1902/jop.2001.72.8.1078.
Nifedipine is used as a long-acting vasodilator, and a primary side effect is the induction of gingival overgrowth, which is characterized by an accumulation of collagenous components within the gingival connective tissue. To elucidate the mechanisms of nifedipine-induced gingival overgrowth, we investigated the effect of nifedipine on Type I collagen metabolism in the gingiva of rats.
Twenty-day-old rats were fed a powdered diet containing or lacking nifedipine for 3 to 55 days. Immunohistochemical analysis with anti-Type I collagen antibody was employed to examine the density of Type I collagen in the gingival connective tissue. Total RNAs were isolated from mandibular molar gingiva on days 0, 3, 15, 30, and 55, and reverse transcription polymerase chain reaction was performed to investigate the mRNA levels of Type I collagen. In addition, we performed a flow cytometric analysis with collagen-coated latex beads and cultured fibroblasts derived from rat gingiva to measure collagen phagocytosis.
Immunohistochemical analysis revealed that Type I collagen was more prevalent in the connective tissue of nifedipine-treated gingiva than in controls on day 55. In the nifedipine-treated group, the expression of Type I collagen mRNA gradually decreased to 1.5% on day 55 compared to day 0. In the control group, Type I collagen mRNA also decreased to 32%; however, mRNA expression was significantly lower in the nifedipine-treated group than in the controls. When the rate of phagocytic cells derived from nifedipine-treated gingiva and controls was represented as the mean +/- SE of the percentage from 3 different experiments, the values were as follows: on day 15, 13.5 +/- 2.1% and 15.0 +/- 1.5%; on day 30, 12.2 +/- 4.3% and 34.5 +/- 6.7% in the nifedipine-treated and the control group, respectively, indicating that phagocytic cells were considerably fewer in the nifedipine-treated gingiva on day 30. This finding demonstrates that the decrease in phagocytosis caused by nifedipine appeared before the detection of severe macroscopic gingival overgrowth.
These findings suggest that the decrease in collagen degradation due to lower phagocytosis is closely associated with the increase in Type I collagen accumulation in nifedipine-treated rat gingiva.
硝苯地平用作长效血管扩张剂，其主要副作用是引起牙龈过度生长，其特征是牙龈结缔组织内胶原成分的蓄积。为阐明硝苯地平诱导牙龈过度生长的机制，我们研究了硝苯地平对大鼠牙龈中I型胶原代谢的影响。
给20日龄大鼠喂食含或不含硝苯地平的粉状饲料3至55天。采用抗I型胶原抗体进行免疫组织化学分析，以检测牙龈结缔组织中I型胶原的密度。在第0、3、15、30和55天从下颌磨牙牙龈分离总RNA，并进行逆转录聚合酶链反应以研究I型胶原的mRNA水平。此外，我们用胶原包被的乳胶珠和源自大鼠牙龈的培养成纤维细胞进行流式细胞术分析，以测量胶原吞噬作用。
免疫组织化学分析显示，在第55天，硝苯地平处理的牙龈结缔组织中I型胶原比对照组更普遍。在硝苯地平处理组中，与第0天相比，I型胶原mRNA的表达在第55天逐渐降至1.5%。在对照组中，I型胶原mRNA也降至32%；然而，硝苯地平处理组中的mRNA表达明显低于对照组。当将源自硝苯地平处理的牙龈和对照组的吞噬细胞率表示为3次不同实验百分比的平均值±标准误时，数值如下：在第15天，分别为13.5±2.1%和15.0±1.5%；在第30天，硝苯地平处理组和对照组分别为12.2±4.3%和34.5±6.7%，表明在第30天硝苯地平处理的牙龈中吞噬细胞明显较少。这一发现表明，硝苯地平引起的吞噬作用降低在检测到严重的宏观牙龈过度生长之前就已出现。
这些发现表明，由于吞噬作用降低导致的胶原降解减少与硝苯地平处理的大鼠牙龈中I型胶原蓄积增加密切相关。
