DEVELOPMENT OF A NOVEL THERAPEUTIC DRUG FOR TREATMENT OF PRETERM DELIVERY

目的：绒毛膜炎（CAM）是早产的一个极其重要的因素，羊水中的各种炎性细胞因子在CAM的发生和宫颈成熟中起重要作用。蛋白多糖（PG）是细胞外基质的主要成分，其抗炎作用受到人们的广泛关注。在这项研究中，PG对炎症细胞因子的影响进行了研究，在LPS刺激培养的成纤维细胞从子宫cervical.Marerials和方法：标本正常人子宫颈后收集子宫肌瘤全子宫切除术在广崎大学医院。将组织切片置于含10%胎牛血清的Dulbecco改良Eagle培养基中，于37℃、5%CO_2/95%空气中培养。在成纤维细胞生长至汇合后，将其在第六代时用于以下实验。将子宫颈成纤维细胞与或 关于我们 在没有蛋白聚糖（0.5mg/ml，lmg/ml）和LPS（lyg/ml）的情况下培养48小时，获得培养基级分。结果：培养的宫颈成纤维细胞在加入LPS后12 h产生IL-1 β，12 h达高峰，随后逐渐下降;在培养细胞的培养基中加入PG以剂量依赖的方式降低IL-1β。1 mg/ml PG和LPS共同孵育，IL-1β抑制率为58%。同一细胞产生的IL-6的量与IL-6的量呈剂量依赖性。与1 mg/ml PG和LPS孵育，IL-6在所有时间与对照相比均显著降低。同一细胞在培养液中产生IL-8的量随时间线性增加，但IL-8的产生随PG浓度的增加而减少。在0.5和1.0 mg/ml PG的存在下，IL-8的产生减少了约20%和30.1%的控制level.Conclusions：目前的研究结果表明，早产可能会受到抑制PG，因为它抑制了各种炎症细胞因子，主要是有助于发病的CAM和宫颈成熟。少

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