Abstract

More and more evidence support the concept that RNA oxidation plays a substantial role in the progress of multiple diseases; however, only a few studies have reported RNA oxidation caused by microbial pathogens. Urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGsn), which are broadly used as indicators of oxidative damage of RNA and DNA, were analyzed in this study to determine which can be used as a biomarker of infection in challenged with Vibrio parahaemolyticus (V. parahaemolyticus). In this work, 24 specific-pathogen-free (SPF) male SD rats were randomly divided into two groups: an infection group and a phosphate-buffered saline (PBS) control group. Our results proved that 8-oxo-Gsn rather than 8-oxo-dGsn was significantly increased after challenged with V. parahaemolyticus in urine and tissue samples of SD rats compared with the PBS control group. Simultaneously, white blood cells (WBCs) counts, intestinal inflammation and inflammatory factors (including CRP, IL-6, IL-1β, TNF-α, IL-10, and IL-17A) were also increased sharply. Which has more clinical value is that the trend of urinary 8-oxo-Gsn was consistent with WBCs, intestinal inflammation and all kinds of inflammatory factors. More importantly is that urinary 8-oxo-Gsn of infection group was positively correlated with WBCs and various inflammatory cytokines. In a word, our results demonstrated that as a systemic RNA oxidation biomarker, we hope 8-oxo-Gsn can be used as a biomarker of the severity of microbial pathogens infection, rather than a specific biomarker of microbial pathogens infection.

摘要

越来越多的证据支持 RNA 氧化在多种疾病的进展中起重要作用的概念；然而，只有少数研究报道了由微生物病原体引起的 RNA 氧化。尿中 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) 和 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn)，它们被广泛用作氧化损伤的指标在本研究中对 RNA 和 DNA 进行了分析，以确定哪些可用作副溶血性弧菌（V. parahaemolyticus）感染的生物标志物）。在这项工作中，将 24 只无特定病原体 (SPF) 雄性 SD 大鼠随机分为两组：感染组和磷酸盐缓冲盐水 (PBS) 对照组。我们的结果证明，在用副溶血性弧菌攻击后，8-oxo-Gsn 而不是 8-oxo-dGsn 显着增加与 PBS 对照组相比，在 SD 大鼠的尿液和组织样本中。同时，白细胞（WBC）计数、肠道炎症和炎症因子（包括 CRP、IL-6、IL-1β、TNF-α、IL-10 和 IL-17A）也急剧增加。更具有临床价值的是，尿8-oxo-Gsn的变化趋势与WBCs、肠道炎症和各种炎症因子一致。更重要的是感染组尿8-oxo-Gsn与WBCs和多种炎性细胞因子呈正相关。总之，我们的结果表明，作为全身性 RNA 氧化生物标志物，我们希望 8-oxo-Gsn 可以作为微生物病原体感染严重程度的生物标志物，而不是微生物病原体感染的特定生物标志物。