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

1. 体内实验：15日龄Fischer大鼠分别饲喂含环孢素A （50-300μg/g）、硝苯地平（200-600μg/g）或地尔硫平（600-6000μg/g）的粉状饲粮40 d。另外两组大鼠同时饲喂含有CsA和其中一种钙阻滞剂的饲料。CsA诱导的GO最严重，其次是硝苯地平和地尔硫卓。联合用药对大鼠氧化石墨烯的诱导作用较单一用药更严重，且呈协同效应。临床观察：监测服用氨氯地平患者牙周状况6个月以上。停用该药可改善患者的牙周状况，但重新使用该药可观察到GO复发。体外实验：硝苯地平对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细胞凋亡的影响。硝苯地平还能抑制LPS刺激下巨噬细胞诱导的no合成酶，提示该药物可抑制成纤维细胞死亡，尤其是炎症牙龈组织。

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.