The effects of selective cyclooxygenase-2 inhibitor on fetal ductus arteriosus and kidney

选择性环氧合酶2抑制剂对胎儿动脉导管和肾脏的影响

• 批准号: 12557086
• 负责人: HARADA Kenji
• 金额: $ 7.87万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557086/
• 关键词: Ductus arteriosus; kidney; Fetus; COX-2 inhibitor; 胎児循環; サイクロオキシゲナーゼ選択的阻害剤; サイクロオキシゲナーゼ; 胎児動脈管; 微少血管灌流

Background : Recent studies demonstrated that selective COX-2 inhibitors constrict the fetal ducus arteriosus (DA) as non-specific COX inhibitors, like indomethacin (IND). We previously reported renal tissue damage in fetal rats induced by maternally administered IND. To evaluate whether a maternally administered selective COX-2 inhibitor, celecoxib, causes morphological renal damages in fetal rats and to evaluate the relation to the fetal DA constriction. Methods : JND (10mg/kg), celecoxibs (10-60mg/kg) and vehicles were administered orally to the pregnant rats on the 20^<th> day of gestation. The fetuses were removed 24 hours after and were divided into two study groups. In the DA constriction study, rapid whole body freezing method was used to obtain the inner diameter ratio of the DA to the main pulmonary artery (DA/PA). In morphological study, the kidneys were removed and examined histopathologically. The data was statistically compared by non-parametric analysis. Result : Celecoxibs constricted the fetal DA dose-dependently (10 mg: 0.92 ± 0.02、20 mg: 0.65 ± 0.12、30 mg: 0.35 ± 0.08、40 mg: 0.31 ± 0.11、50mg: 0.17 ± 0.10、 60 mg: 0.11 ± 0.04). Celecoxibs produced a variety of corticomedullary necrosis and of collapse in distal and proximal tubules in the fetal kidney. IND produced the similar but more severe morphological damages. Conclusion : These data suggested that a selective COX-2 inhibitor, celecoxib, causes morphological tissue damages in fetal rats, like indomethacin, and that these damages are indepen of the fetal DA constriction.

背景：最近的研究表明，选择性COX-2抑制剂将胎儿ducus Arteriosus（DA）限制为非特异性COX抑制剂，例如吲哚美辛（IND）。我们先前报道了由母体施用的IND诱导的胎儿大鼠肾脏组织损伤。为了评估主要管理的选择性COX-2抑制剂Celecoxib是否会导致胎儿大鼠的形态肾脏损害，并评估与胎儿DA收缩的关系。方法：JND（10mg/kg），塞来昔布（10-60mg/kg）和车辆在妊娠20^<th>日期向怀孕的大鼠口服。 24小时后，将胎儿移除，并分为两个研究组。在DA收缩研究中，使用快速的全身冷冻方法来获得DA与主肺动脉（DA/PA）的内径比。在形态学研究中，将孩子们删除并在组织病理学上检查。通过非参数分析比较了数据。结果：塞来毒素限制了胎儿DA剂量依赖性（10 mg：0.92±0.02，20 mg：0.65±0.12，30 mg：0.35±0.08，40 mg：0.31±0.11，50 mg：0.17±0.10，60 mg：0.10 mg：0.11±0.11±0.04）。塞来昔布在胎儿肾脏中产生了多种皮质甲付运坏死，并在盘中和近端管中塌陷。 IND产生了类似但更严重的形态损害。结论：这些数据表明，选择性COX-2抑制剂Celecoxib会导致胎儿大鼠（如吲哚美辛）的形态组织损害，并且这些损害是胎儿DA限制的独立。