PROBLEM The Brown Norway (BN) rat is a model of T-helper 2 immune diseases, and also a model of pregnancy disorders that include placental insufficiency, fetal loss, and pre-eclampsia-like symptoms. The aim of this study was to investigate the plasma proteomic/cytokine profile of pregnant BN rats in comparison to that of the Lewis (LEW) rat strain. METHOD OF STUDY Plasma proteomics differences were studied at day 13 of pregnancy in pooled plasma samples by differential in-gel electrophoresis, and protein identification was performed by mass spectrometry. Key protein findings and predicted cytokine differences were validated by ELISA using plasma from rats at various pregnancy stages. Proteomics data were used for ingenuity pathway analysis (IPA). RESULTS In-gel analysis revealed 74 proteins with differential expression between BN and LEW pregnant dams. ELISA studies confirmed increased maternal plasma levels of complement 4, prothrombin, and C-reactive protein in BN compared to LEW pregnancies. LEW pregnancies showed higher maternal plasma levels of transthyretin and haptoglobin than BN pregnancies. Ingenuity pathway analysis revealed that BN pregnancies are characterized by activation of pro-coagulant, reactive oxygen species, and immune-mediated chronic inflammation pathways, and suggested increased interleukin 6 and decreased transforming growth factor-β1 as potential upstream events. Plasma cytokine analysis revealed that pregnant BN dams have a switch from anti- to pro-inflammatory cytokines with the opposite switch observed in pregnant LEW dams. CONCLUSION Brown Norway rats show a maternal pro-inflammatory response to pregnancy that likely contributes to the reproductive outcomes observed in this rat strain.

中文翻译：

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妊娠并发症大鼠模型中的母体血浆蛋白质组学揭示了免疫和促凝血基因通路的激活。

问题 Brown Norway (BN) 大鼠是T-helper 2 免疫疾病的模型，也是包括胎盘功能不全、胎儿丢失和先兆子痫样症状的妊娠疾病模型。本研究的目的是研究与 Lewis (LEW) 大鼠品系相比，怀孕 BN 大鼠的血浆蛋白质组学/细胞因子谱。研究方法 在妊娠第 13 天，通过差异凝胶电泳研究混合血浆样品中血浆蛋白质组学的差异，并通过质谱法进行蛋白质鉴定。使用来自不同妊娠阶段大鼠的血浆，通过 ELISA 验证了关键蛋白质发现和预测的细胞因子差异。蛋白质组学数据用于独创性途径分析（IPA）。结果 凝胶内分析揭示了 74 种蛋白质在 BN 和 LEW 妊娠母鼠之间具有差异表达。ELISA 研究证实，与 LEW 妊娠相比，BN 中补体 4、凝血酶原和 C 反应蛋白的母体血浆水平升高。与 BN 妊娠相比，LEW 妊娠显示出更高的母体血浆转甲状腺素蛋白和结合珠蛋白水平。Ingenuity 通路分析显示，BN 妊娠的特征是促凝剂、活性氧和免疫介导的慢性炎症通路的激活，并表明白细胞介素 6 增加和转化生长因子-β1 减少是潜在的上游事件。血浆细胞因子分析显示，怀孕的 BN 水坝具有从抗炎细胞因子到促炎细胞因子的转换，而在怀孕的 LEW 水坝中观察到相反的转换。