Department for Companion Animals, Small Animal Internal Medicine, University of Veterinary Medicine, Vienna, Austria.
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
PLoS One. 2024 Feb 8;19(2):e0297924. doi: 10.1371/journal.pone.0297924. eCollection 2024.
Acute haemorrhagic diarrhoea is a common complaint in dogs. In addition to causes like intestinal parasites, dietary indiscretion, intestinal foreign bodies, canine parvovirus infection, or hypoadrenocorticism, acute haemorrhagic diarrhoea syndrome (AHDS) is an important and sometimes life-threatening differential diagnosis. There is some evidence supporting the link between Clostridium perfringens toxins and AHDS. These toxins may be partially responsible for the epithelial cell injury, but the pathogenesis of AHDS is still not fully understood. Recent studies have suggested that severe damage to the intestinal mucosa and associated barrier dysfunction can trigger chronic gastrointestinal illnesses. Besides bloodwork and classical markers for AHDS such as protein loss and intestinal bacterial dysbiosis, we focused mainly on the plasma-proteome to identify systemic pathological alterations during this disease and searched for potential biomarkers to improve the diagnosis. To accomplish the goals, we used liquid chromatography-mass spectrometry. We compared the proteomic profiles of 20 dogs with AHDS to 20 age-, breed-, and sex-matched control dogs. All dogs were examined, and several blood work parameters were determined and compared, including plasma biochemistry and cell counts. We identified and quantified (relative quantification) 207 plasmatic proteins, from which dozens showed significantly altered levels in AHDS. Serpina3, Lipopolysaccharide-binding protein, several Ig-like domain-containing proteins, Glyceraldehyde-3-phosphate dehydrogenase and Serum amyloid A were more abundant in plasma from AHDS affected dogs. In contrast, other proteins such as Paraoxonase, Selenoprotein, Amine oxidases, and Apolipoprotein C-IV were significantly less abundant. Many of the identified and quantified proteins are known to be associated with inflammation. Other proteins like Serpina3 and RPLP1 have a relevant role in oncogenesis. Some proteins and their roles have not yet been described in dogs with diarrhoea. Our study opens new avenues that could contribute to the understanding of the aetiology and pathophysiology of AHDS.
急性出血性腹泻是犬的常见病症。除了肠道寄生虫、饮食不当、肠道异物、犬细小病毒感染或肾上腺皮质功能减退等原因外，急性出血性腹泻综合征（AHDS）也是一个重要的、有时甚至危及生命的鉴别诊断。有一些证据表明产气荚膜梭菌毒素与 AHDS 之间存在关联。这些毒素可能部分导致了上皮细胞损伤，但 AHDS 的发病机制仍不完全清楚。最近的研究表明，肠道黏膜的严重损伤和相关的屏障功能障碍可能引发慢性胃肠道疾病。除了血液检查和 AHDS 的经典标志物，如蛋白质丢失和肠道细菌失调，我们主要关注血浆蛋白质组，以确定在这种疾病过程中发生的全身病理变化，并寻找潜在的生物标志物来改善诊断。为了实现这些目标，我们使用了液相色谱-质谱联用技术。我们将 20 只患有 AHDS 的犬与 20 只年龄、品种和性别匹配的对照犬的蛋白质组图谱进行了比较。对所有犬进行了检查，并确定和比较了几种血液参数，包括血浆生化和细胞计数。我们鉴定和量化了（相对定量）207 种血浆蛋白，其中数十种在 AHDS 中表现出明显改变的水平。AHDS 受影响犬的血浆中，Serpina3、脂多糖结合蛋白、几种 Ig 样结构域蛋白、甘油醛-3-磷酸脱氢酶和血清淀粉样蛋白 A 的含量较高。相比之下，其他蛋白质如对氧磷酶、硒蛋白、胺氧化酶和载脂蛋白 C-IV 的含量则明显较低。许多鉴定和量化的蛋白质已知与炎症有关。Serpina3 和 RPLP1 等其他蛋白质在肿瘤发生中具有重要作用。一些蛋白质及其作用在患有腹泻的犬中尚未被描述。我们的研究开辟了新的途径，有助于理解 AHDS 的病因和病理生理学。
