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92 KDA TYPE IV COLLAGENASE INCREASES DURING EXPERIMENTAL INTRAUTERINE INFECTION

92 KDA TYPE IV COLLAGENASE INCREASES DURING EXPERIMENTAL INTRAUTERINE INFECTION
92 实验性宫内感染期间 KDA IV 型胶原酶增加
批准号:
6247233
负责人:
MILES J. NOVY
金额:
$4.86万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-05-01 至 1998-04-30

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中文摘要
翻译
产妇生殖道感染与 胎膜早破与早产的关系 劳力。已有研究表明,感染会触发一种细胞因子 参与胎膜早破发病的级联反应。最近,我们 基质金属蛋白酶(MMPs)在卵巢癌组织中的过度表达 肿瘤坏死因子-`诱导人羊膜源性细胞。 MMPs在绒毛膜中的表达增加被认为是一种 舞会的机制。三只怀孕的恒河猴被慢性 于妊娠第120天插管。感染是通过以下方式确定的 经绒毛蜕膜导管接种B组链球菌。 连续采集前、后羊水样本 细菌接种。样品用凝胶底物分析。 酶谱和蛋白质印迹。92 kDa的无活性形式和83 kDa的活性形式 感染后24小时羊水中有基质金属蛋白酶9的表达。这个 92 kDa和83 kDa形式的量/活性与 接种剂量,当羊水中存在细菌时,接种量更高 流体。高分子量二聚体的存在是其特征 感染启动的基质金属蛋白酶-9诱导。72 kDa-IV型血清白蛋白水平 胶原酶与金属蛋白酶组织抑制物 (TIMP-1)不受感染的影响。这些发现支持 羊水内感染和羊水过少之间存在分子联系 毕业舞会。存在宫内感染和羊水增加 细胞因子与较高数量的基质金属蛋白酶-9相关。增强的 细胞外基质降解会使绒毛羊膜变弱 最后是毕业舞会的出现。
英文摘要
Maternal genital tract infections have been associated with the development of premature rupture of the membranes (PROM) and preterm labor. It has been suggested that infection triggers a cytokine cascade that participates in the pathogenesis of PROM. Recently, we demonstrated the overexpression of matrix metalloproteinases (MMPs) in human amnion-derived cells induced by tumor necrosis factor (TNF-`). Increased expression of MMPs in chorioamnion has been proposed as a mechanism of PROM. Three pregnant rhesus monkeys were chronically catheterized at day 120 of gestation. Infection was established by inoculation of group B streptococci through a choriodecidual catheter. Amniotic fluid (AF) samples were collected serially before and after bacterial inoculation. Samples were analyzed by gel-substrate zymography and Western blot. A 92 kDa inactive form and 83 kDa active MMP-9 appeared in amniotic fluid 24 hr following infection. The amount/activity of 92 and 83 kDa forms showed a dependance on the inoculum dose and was higher when bacteria were present in amniotic fluid. Presence of high molecular weight dimers was characteristic of infection-initiated MMP-9 induction. The levels of 72 kDa type-IV collagenase (MMP-2) and tissue inhibitor of metalloproteinases (TIMP-1) were not modified by infection. These findings support the existence of a molecular link between intraamniotic infection and PROM. Presence of intrauterine infection and increased amniotic fluid cytokines correlates with higher amounts of MMP-9. Augmented extracellular matrix degradation will condition chorioamnion weakening and eventually the appearance of PROM.
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