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利用 LC-MS/MS 在马脓毒性关节炎实验模型中发现用于检测感染清除的潜在标志物的蛋白质组学。

Discovery proteomics for the detection of putative markers for eradication of infection in an experimental model of equine septic arthritis using LC-MS/MS.

机构信息

Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada.

Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada.

出版信息

J Proteomics. 2022 Jun 15;261:104571. doi: 10.1016/j.jprot.2022.104571. Epub 2022 Mar 26.

DOI:10.1016/j.jprot.2022.104571
PMID:35346876
Abstract

Septic arthritis (SA) is a life-threatening condition in horses, and identifying eradication of infection in equine SA is challenging. This study explored the discovery of putative biomarkers for the eradication of joint infection in horses. We performed proteomics analysis of synovial fluid (SF) and plasma from horses with experimental SA, non-septic lipopolysaccharide-induced arthritis, and controls. The point of eradication of infection in horses with SA was determined previously. We compared spectral intensities between groups as well as before and after the eradication of infection. Twenty-six differentially abundant proteins were identified, which were upregulated in SF of horses with SA compared to the other groups, as well as compared to the same horses post-eradication of infection. In plasma, we did not identify differentially abundant proteins. Differentially abundant proteins in SF were of cellular origin and their biological functions included ubiquitination, signal transduction, apoptosis etc. The difference in their relative abundance between experimental groups was ≥10-fold compared to the abundance expected based on the difference in cell count alone (2-fold). Since most of cells in joints with bacterial infection are neutrophils, we suggest that the variable abundance of neutrophil- and cell-associated proteins represent potential biomarkers of eradication of infection in equine SA. SIGNIFICANCE: Septic arthritis is an important condition in horses, which can be life-threatening. At present, identifying eradication of infection in cases of equine septic arthritis is challenging. In this study, we performed a global proteomics analysis of synovial fluid and plasma in horses with experimental septic arthritis and identified 26 differentially abundant proteins compared to non-septic arthritis and post eradication of infection. The results of this study provide the basis for further characterization of the differentially abundant proteins and identification of clinically relevant biomarkers of septic arthritis in horses.

摘要

脓毒性关节炎(SA)是一种危及生命的马病,确定马的 SA 关节感染是否已根除具有挑战性。本研究探索了鉴定马关节感染根除的潜在生物标志物的方法。我们对患有实验性 SA、非脓毒性脂多糖诱导性关节炎和对照马的关节滑液(SF)和血浆进行了蛋白质组学分析。此前已经确定了 SA 马感染根除的时间点。我们比较了组间以及感染根除前后的光谱强度。鉴定出 26 个差异丰度蛋白,与其他组相比,这些蛋白在 SA 马的 SF 中上调,与感染根除后的同一匹马相比也上调。在血浆中,我们没有鉴定出差异丰度蛋白。SF 中的差异丰度蛋白具有细胞起源,其生物学功能包括泛素化、信号转导、细胞凋亡等。与单独基于细胞计数的差异相比(2 倍),实验组之间的相对丰度差异≥10 倍。由于受细菌感染的关节中的大多数细胞是中性粒细胞,我们推测中性粒细胞和细胞相关蛋白的可变丰度可能代表马 SA 感染根除的潜在生物标志物。意义:脓毒性关节炎是一种重要的马病,可能危及生命。目前,确定马脓毒性关节炎的感染是否已根除具有挑战性。在这项研究中,我们对患有实验性脓毒性关节炎的马的关节滑液和血浆进行了全面蛋白质组学分析,与非脓毒性关节炎和感染根除后相比,鉴定出 26 个差异丰度蛋白。本研究结果为进一步鉴定差异丰度蛋白和鉴定马脓毒性关节炎的临床相关生物标志物提供了基础。

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