Yang Qing, Whitin John C, Ling Xuefeng Bruce, Nayak Nihar R, Cohen Harvey J, Jin Joseph, Schilling James, Yu Tom To-Sang, Madan Ashima
Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
Pediatr Res. 2009 Jul;66(1):11-6. doi: 10.1203/PDR.0b013e3181a207e3.
Preterm labor (PTL) is frequently associated with inflammation. We hypothesized that biomarkers during pregnancy can identify pregnancies most at risk for development of PTL. An inflammation-induced mouse model of PTL was used. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to analyze and compare the plasma protein (PP) profile between CD-1 mice injected intrauterine with either lipopolysaccharide (LPS) or PBS on d 14.5 of gestation. The median differences of normalized PP peaks between the two groups were determined using the Mann-Whitney U test and the false discovery rate. In a second series of experiments, both groups of mice were injected with a lower dose of LPS. A total of 1665 peaks were detected. Thirty peaks were highly differentially expressed (p < 0.0001) between the groups. Two 11 kDa protein peaks were identified by MALDI-TOF/TOF-MS and confirmed to be mouse serum amyloid A (SAA) 1 and 2. Plasma SAA2 levels were increased in LPS-treated animals compared with controls and in LPS-treated animals that delivered preterm vs. those that delivered at term. SAA2 has the potential to be a plasma biomarker that can identify pregnancies at risk for development of PTL.
早产（PTL）常与炎症相关。我们推测孕期生物标志物可识别发生PTL风险最高的妊娠。使用了炎症诱导的PTL小鼠模型。在妊娠第14.5天，对宫内注射脂多糖（LPS）或磷酸盐缓冲液（PBS）的CD-1小鼠，采用表面增强激光解吸/电离飞行时间质谱分析并比较其血浆蛋白（PP）谱。使用曼-惠特尼U检验和错误发现率确定两组之间标准化PP峰的中位数差异。在第二系列实验中，两组小鼠均注射较低剂量的LPS。共检测到1665个峰。两组之间有30个峰高度差异表达（p < 0.0001）。通过基质辅助激光解吸电离飞行时间串联质谱（MALDI-TOF/TOF-MS）鉴定出两个11 kDa蛋白峰，证实为小鼠血清淀粉样蛋白A（SAA）1和2。与对照组相比，LPS处理动物的血浆SAA2水平升高，且早产的LPS处理动物与足月分娩的动物相比血浆SAA2水平也升高。SAA2有可能成为一种血浆生物标志物，可识别有发生PTL风险的妊娠。
