Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
Vet Immunol Immunopathol. 2022 Jan;243:110361. doi: 10.1016/j.vetimm.2021.110361. Epub 2021 Nov 18.
Endotoxemia is one of the most common inflammatory situations leading to death of ruminants. Owing to the importance of this condition, several therapeutic regimens have been proposed, evaluated and implemented to treat endotoxemia. It has recently been suggested that low molecular weight heparin may be effective in treating endotoxemia. Thus, the present experimental study was conducted to evaluate the acute phase response and multiple organ dysfunction following the treatment of the Ovine experimental endotoxemia model employing this compound. In this regard, 20 clinically healthy 1-year old Iranian fat-tailed ewes were randomly divided into 4 equal groups, comprising LMWH 50, LMWH 100, Ctrl+, and Ctrl-. Lipopolysaccharide from Escherichia coli serotype O55:B5 at 0.4 μg/kg was intravenously administered to the ewes. Low molecular weight heparin (at 50 and 100 IU/kg) was administrated to LMWH 50 and LMWH 100 groups, respectively. Positive control (Ctrl+) received lipopolysaccharide and treated only by intravenous fluid without any drugs, and negative control (Ctrl-) only received intravenous fluids without lipopolysaccharide or any drugs. All the ewes were clinically evaluated before and 1.5, 3, 4.5, 6 and 24 h after lipopolysaccharide injection, and blood samplings were also performed at those hours. Serum concentrations of serum amyloid A, tumor necrosis factor-alpha, superoxide dismutase, glutathione peroxidase, creatine kinase-MB, homocysteine, total bilirubin, aspartate aminotransferase, and creatinine were measured. Serum concentrations of acute phase proteins, inflammatory cytokines, oxidative stress, cardiovascular, hepatic and renal biomarkers, and clinical parameters were significantly increased following the induction of endotoxemia in the groups receiving lipopolysaccharide. Significantly lower concentration of these markers was observed at 4.5 and 6 h after lipopolysaccharide administration in the sheep treated with LMWH compared to the Ctrl + group. In conclusion, low molecular weight heparin could act as an anti-inflammatory drug by decreasing cytokines and acute phase proteins, modulating oxidative stress biomarkers, and by reducing multiple organ dysfunction following the induction of endotoxemia by Escherichia coli serotype O55:B5 in Iranian fat-tailed sheep in a dose-dependent manner. Furthermore, the anti-inflammatory effects of low molecular weight heparin at 100 IU/kg were significantly higher than 50 IU/kg in the treatment of endotoxemic sheep.
内毒素血症是导致反刍动物死亡的最常见炎症情况之一。由于这种情况的重要性，已经提出、评估和实施了几种治疗方案来治疗内毒素血症。最近有人提出，低分子量肝素可能对治疗内毒素血症有效。因此，本实验研究旨在评估在使用该化合物治疗绵羊实验性内毒素血症模型后，急性相反应和多器官功能障碍。为此，将 20 只临床健康的 1 岁伊朗脂肪尾羊随机分为 4 个相等的组，包括 LMWH 50、LMWH 100、Ctrl+和 Ctrl-。将大肠杆菌 O55:B5 型脂多糖以 0.4μg/kg 的剂量静脉内给予绵羊。LMWH 50 和 LMWH 100 组分别给予低分子量肝素（50 和 100IU/kg）。阳性对照（Ctrl+）仅接受脂多糖和静脉输液治疗，而无任何药物治疗，阴性对照（Ctrl-）仅接受静脉输液，无脂多糖或任何药物。所有绵羊在注射脂多糖前和 1.5、3、4.5、6 和 24 小时后进行临床评估，并在这些时间点进行血液取样。测量血清淀粉样蛋白 A、肿瘤坏死因子-α、超氧化物歧化酶、谷胱甘肽过氧化物酶、肌酸激酶-MB、同型半胱氨酸、总胆红素、天门冬氨酸氨基转移酶和肌酐的血清浓度。脂多糖诱导后，接受脂多糖的各组的急性期蛋白、炎症细胞因子、氧化应激、心血管、肝和肾生物标志物和临床参数的血清浓度显著升高。与 Ctrl+组相比，在脂多糖给药后 4.5 和 6 小时，用 LMWH 治疗的绵羊这些标志物的浓度明显较低。总之，低分子量肝素可通过降低细胞因子和急性期蛋白、调节氧化应激生物标志物以及降低由大肠杆菌 O55:B5 诱导的内毒素血症后多器官功能障碍，在伊朗脂肪尾羊中发挥抗炎作用，且呈剂量依赖性。此外，低分子量肝素 100IU/kg 的抗炎作用明显高于治疗内毒素血症绵羊的 50IU/kg。
