DEVELOPMENT OF A NOVEL THERAPEUTIC DRUG FOR TREATMENT OF PRETERM DELIVERY

开发治疗早产的新型治疗药物

基本信息

批准号：
18591791
负责人：
TANAKA Kanji
金额：
$ 1.58万
依托单位：
Hirosaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Objectives: Chorioamnionitis (CAM) is an extremely important factor in preterm delivery, and various inflammatory cytokines of amnionic fluid have important roles in the onset of CAM and cervical ripening. Proteoglycan (PG) was a main component of the extracellular matrix and its anti-inflammatory effects have attracted particular attention. In this study, the effect of PG on inflammatory cytokines was investigated in LPS-stimulated cultured fibroblasts from the uterine cervix.Marerials and Methods: A specimen of normal human uterine cervix was collected after a total hysterectomy for uterine myoma at Hirosaki University Hospital. This tissue sample was cut into small pieces, which were then incubated in Dulbecco's modified Eagle medium containing 10% fetal bovine serum in a humidified atmosphere 5% CO_2/95% air at 37℃. After the fibroblasts had grown to confluency, they were used at up to sixth passage for the following experiments. Uterine cervical fibroblasts were incubated with or … More without Proteoglycan (0.5 mg/ml, 1 mg/ml) and LPS (1 μ g/ml) for 48 h, and a medium fraction was obtained. The amounts of IL-1β, IL-6 and IL-8 in the medium were assayed by the ELISA method.Results: In the medium, the amount of IL-1β produced by cultured fibroblasts from the uterine cervix increased and reached a peak 12 hours after the addition of LPS, but later this amount decreased gradually. The addition of PG to the medium of cultured cells reduced IL-1β in a dose-dependent manner. Incubated with 1 mg/ml PG and LPS, IL-1β was suppressed by 58% compared with the controls. The amount of IL-6 produced by the same cell in the amount of IL-6 in a dose-dependent manner. Incubated with 1 mg/ml PG and LPS, IL-6 was significantly decreased in comparison with the controls at all times. The amount of IL-8 produced by the same cell in the medium increased linearly with time, but IL-8 production decreased with an increase in PG concentration. In the presence of 0.5 and 1.0 mg/ml PG, IL-8 production was decreased by about 20% and 30.1% of the control level.Conclusions: The results of the current study indicate that preterm delivery may be suppressed by PG since it inhibited various inflammatory cytokines that mainly contribute to the onset of CAM and cervical ripening. Less

目标：绒毛膜膜炎（CAM）是早产的极其重要的因素，羊水液的各种炎症细胞因子在CAM和宫颈成熟的发作中具有重要作用。蛋白聚糖（PG）是细胞外基质的主要组成部分，其抗炎作用引起了特别的关注。在这项研究中，PG对子宫宫颈的LPS刺激的培养的成纤维细胞研究了PG对炎性细胞因子的作用：肉疗和方法：在息肉科大学医院的子宫肾上腺肌瘤全滞术后，收集了正常人子宫宫颈的标本。将该组织样品切成小块，然后将其在Dulbecco的改良鹰培养基中孵育，该型含有10％的胎牛血清，在37℃下为5％CO_2/95％空气中的5％CO_2/95％空气。成纤维细胞逐渐融合后，它们在以下实验中最多可用于第六通道。将子宫宫颈成纤维细胞与或……没有蛋白聚糖（0.5 mg/ml，1 mg/ml）和LPS（1μg/ml）的更多或更多的……持续48小时，并获得培养基分数。培养基中的IL-1β，IL-6和IL-8的量是通过ELISA方法分配的。分析：在培养基中，由子宫颈培养的成纤维细胞产生的IL-1β量增加并增加了LPS后12小时的峰值，但后来又逐渐减少。在培养细胞的培养基中添加Pg以剂量依赖性方式降低了IL-1β。与对照组相比，IL-1β与1 mg/mL PG和LPS孵育，IL-1β被抑制58％。同一细胞以剂量依赖性方式以IL-6产生的IL-6量。与1 mg/mL PG和LPS一起孵育，与对照相比，IL-6显着降低。同一细胞在培养基中产生的IL-8量随时间线性增加，但随着PG浓度的增加，IL-8产生降低。在存在0.5和1.0 mg/mL PG的情况下，IL-8产生的产生约为对照水平的20％和30.1％。结论：当前研究的结果表明，PG可以抑制早产，因为它主要抑制各种炎症细胞因子，主要抑制了CAM和宫颈酸化的发作。较少的