Haniastuti T, Santoso A Supartinah, Agustiono P, Agustina D, Sosroseno W
Department of Oral Biology, Faculty of Dentistry, Gadjah Mada University, Yogyakarta, Indonesia.
Biomed Pharmacother. 2002 Jul;56(5):235-40. doi: 10.1016/s0753-3322(02)00183-x.
The aim of the present study was to determine the profile of p53 protein expression in gingival tissues after treatment with nifedipine in rats. Rats were treated daily by gastric intubation with or without DMSO alone or DMSO-dissolved nifedipine at concentrations of 15, 30 or 60 mg/kg body weight for 1, 3 or 6 week(s). Gingival width and height were measured macroscopically. Monoclonal antibodies recognizing both wild-type and mutant p53 protein were applied on paraffin-embedded gingival sections using microwave pretreatment and immunohistochemical methods. The gingival width and height were increased in the animals treated with nifedipine at concentrations of 30 and 60 mg/kg body weight. Increased gingival width and height were already seen in the animals treated with 60 mg of nifedipine for 1 week, whereas treatments with 30 mg of nifedipine resulted in increased gingival width and height after treatment for at least 3 weeks. The expression of p53 protein was elevated in the animals treated with 30 or 60 mg of nifedipine. Treatments with nifedipine at the concentration of 60 mg/kg body weight for 1 week induced the expression of p53 protein in the gingival tissues. Treatment with nifedipine in rats led to the inducement of gingival hyperplasia and increase in the numbers of p53-positive gingival epithelial cells by a dose and frequency dependent mechanism, suggesting that p53 protein may play a crucial role in the regulation of nifedipine-induced gingival hyperplasia.
本研究的目的是确定大鼠经硝苯地平治疗后牙龈组织中p53蛋白的表达情况。大鼠每天经胃插管给予单独的二甲基亚砜(DMSO)或溶解于DMSO的硝苯地平,浓度分别为15、30或60mg/kg体重,持续1、3或6周。宏观测量牙龈宽度和高度。使用微波预处理和免疫组织化学方法,将识别野生型和突变型p53蛋白的单克隆抗体应用于石蜡包埋的牙龈切片。体重为30和60mg/kg的硝苯地平处理组动物的牙龈宽度和高度增加。60mg硝苯地平处理1周的动物已出现牙龈宽度和高度增加,而30mg硝苯地平处理至少3周后才出现牙龈宽度和高度增加。30或60mg硝苯地平处理组动物的p53蛋白表达升高。体重为60mg/kg的硝苯地平处理1周可诱导牙龈组织中p53蛋白的表达。大鼠经硝苯地平治疗导致牙龈增生,并通过剂量和频率依赖性机制增加p53阳性牙龈上皮细胞数量,提示p53蛋白可能在硝苯地平诱导的牙龈增生调节中起关键作用。