目的:为了确定各种炎症/免疫的浓度是否改变,急性期-,细胞外基质-,粘连-,羊水(AF)中的丝氨酸蛋白酶相关蛋白与微生物侵入羊膜腔和/或羊膜腔内炎症(MIAC/IAI)独立相关,即将发生的自发性早产(SPTD;≤7天),早期早产胎膜破裂(PPROM)妇女的主要新生儿发病率/死亡率(NMM)。
方法:这是一项回顾性队列研究,涉及111例接受羊膜穿刺术诊断MIAC/IAI的PPROM(24-31周)单胎孕妇。通过酶联免疫吸附测定(ELISA)在储存的AF样品中测量以下蛋白质:APRIL,DKK-3,Gal-3BP,IGFBP-2,IL-8,VDBP,Lumican,MMP-2,MMP-8,SPARC,TGFBI,TGF-β1,E-选择素,ICAM-5,P-选择素,触珠蛋白,铁调素,SAA1,kallistatin,UPA。
结果:多变量逻辑回归分析显示(i)APRIL升高,IL-8、MMP-8和TGFBI在房颤中的水平,降低了AF中的Lumican和SPARC水平,高百分比的AFTGF-β1和uPA定量下限以上的样本与MIAC/IAI显著相关;(ii)IL-8和MMP-8水平升高与SPTD在7天内显著相关;(iii)AFIL-6水平升高与主要NMM风险增加显著相关,当调整基线协变量时。
结论:ECM(lumican,SPRAC,TGFBI,AF中TGF-β1)和丝氨酸蛋白酶(uPA)相关蛋白参与宿主对羊膜腔感染/炎症反应的调节,而房颤炎症(IL-8、MMP-8和IL-6)相关介质与早产和早期PPROM中主要NMM的发生有关。
OBJECTIVE: To determine whether altered concentrations of various inflammation/immune-, acute phase-, extracellular matrix-, adhesion-, and serine protease-related proteins in the amniotic fluid (AF) are independently associated with microbial invasion of the amniotic cavity and/or intra-amniotic inflammation (MIAC/IAI), imminent spontaneous preterm delivery (SPTD; ≤7 days), and major neonatal morbidity/mortality (NMM) in women with early preterm prelabor rupture of membranes (PPROM).
METHODS: This was a retrospective cohort study involving 111 singleton pregnant women with PPROM (24-31 weeks) undergoing amniocentesis to diagnose MIAC/IAI. The following proteins were measured in stored AF samples by enzyme-linked immunosorbent assay (ELISA): APRIL, DKK-3, Gal-3BP, IGFBP-2, IL-8, VDBP, lumican, MMP-2, MMP-8, SPARC, TGFBI, TGF-β1, E-selectin, ICAM-5, P-selectin, haptoglobin, hepcidin, SAA1, kallistatin, and uPA.
RESULTS: Multivariate logistic regression analyses revealed that (i) elevated APRIL, IL-8, MMP-8, and TGFBI levels in the AF, reduced lumican and SPARC levels in the AF, and high percentages of samples above the lower limit of quantification for AF TGF-β1 and uPA were significantly associated with MIAC/IAI; (ii) elevated AF levels of IL-8 and MMP-8 were significantly associated with SPTD within 7 days; and (iii) elevated AF IL-6 levels were significantly associated with increased risk for major NMM, when adjusted for baseline covariates.
CONCLUSIONS: ECM (lumican, SPRAC, TGFBI, and TGF-β1)- and serine protease (uPA)-associated proteins in the AF are involved in the regulation of the host response to infection/inflammation in the amniotic cavity, whereas AF inflammation (IL-8, MMP-8, and IL-6)-associated mediators are implicated in the development of preterm parturition and major NMM in early PPROM.