Yu Do-Hyeon, Kim Bumseok, Park Jinho
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA.
J Vet Med Sci. 2012 May;74(5):537-44. doi: 10.1292/jvms.11-0321. Epub 2011 Dec 6.
In this study, the pathophysiologic and immunologic parameters from a 24-hr of canine endotoxemia model by lipopolysaccharide (LPS) infusion were evaluated. For that, twelve healthy beagles received a continuous 24-hr IV infusion of low dose LPS (10 µg/kg/h, from Escherichia coli serotype O111:B4) dissolved in saline. Complete blood counts and serum biochemical analysis as well as histopathologic examination were performed to assess pathophysiologic changes such as neutrophil migration and organ injury. To evaluate immunologic parameters, the concentrations of plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were determined, and neutrophil activation was also evaluated based on cell surface expression of CD11b using flow cytometry analysis. As results, systemic signs of endotoxemia including fever, vomiting, and hemorrhagic diarrhea were observed within short time after LPS infusion. Severe leukopenia and increased fluorescent intensity of CD11b on neutrophils were observed at 3 hr while percent positive of CD11b was the maximum at 12 hr during the experiment. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) concentrations increased markedly, and organ damage was confirmed on histopathologic examination. Plasma TNF-α peaked at 3 hr and decreased rapidly, while the concentrations of IL-6 and IL-10 increased gradually until 6 hr and decreased thereafter. Using this canine endotoxemia model, we were able to determine the kinetics of pathophysiologic and immunologic parameters over a period of 24 hr. This study will enhance our understanding of their mechanisms underlying canine sepsis.
在本研究中，对通过输注脂多糖（LPS）建立的犬24小时内毒素血症模型的病理生理和免疫参数进行了评估。为此，12只健康的比格犬接受了持续24小时的低剂量LPS（10μg/kg/h，来自大肠杆菌O111:B4血清型）静脉输注，LPS溶解于盐水中。进行了全血细胞计数、血清生化分析以及组织病理学检查，以评估诸如中性粒细胞迁移和器官损伤等病理生理变化。为了评估免疫参数，测定了血浆肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和IL-10的浓度，并使用流式细胞术分析基于CD11b的细胞表面表达评估中性粒细胞活化。结果显示，在LPS输注后的短时间内观察到内毒素血症的全身症状，包括发热、呕吐和出血性腹泻。在实验期间，3小时时观察到严重白细胞减少以及中性粒细胞上CD11b荧光强度增加，而CD11b阳性百分比在12小时时最高。血浆丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）、乳酸脱氢酶（LDH）和肌酸磷酸激酶（CPK）浓度显著升高，并且组织病理学检查证实了器官损伤。血浆TNF-α在3小时达到峰值并迅速下降，而IL-6和IL-10的浓度在6小时前逐渐升高，此后下降。使用该犬内毒素血症模型，我们能够确定24小时内病理生理和免疫参数的动力学变化。本研究将增强我们对犬脓毒症潜在机制的理解。
