Department of Clinical Pharmacy and Healthcare Science, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.
Department of Pharmacy, Ishikawa Prefectural Central Hospital, 2-1 Kuratsukihigashi, Kanazawa, Ishikawa, 920-8530, Japan.
Int J Hematol. 2021 Aug;114(2):172-178. doi: 10.1007/s12185-021-03158-y. Epub 2021 Apr 27.
Lipopolysaccharide (LPS) and tissue factor (TF) have frequently been used to induce disseminated intravascular coagulation (DIC) in experimental animal models. We have previously reported that the pathophysiology of DIC differs according to the inducing agents. However, inflammatory status and bleeding symptoms have not been fully compared between rat models of the two forms of DIC. We attempted to evaluate detailed characteristic features of LPS- and TF-induced DIC models, especially in regard to inflammatory status and bleeding symptoms, in addition to selected hemostatic parameters and pathologic findings in the kidneys. The degree of hemostatic activation in both types of experimental DIC was identical, based on the results of thrombin-antithrombin complex levels. Markedly elevated tumor necrosis factor, interleukin-6, and high-mobility group box-1 concentrations were observed with severe organ dysfunction and marked fibrin deposition in the kidney on administration of LPS, whereas markedly elevated D-dimer concentration and bleeding symptoms were observed with TF administration. Pathophysiology such as fibrinolytic activity, organ dysfunction, inflammation status, and bleeding symptom differed markedly between LPS- and TF-induced DIC models in rats. We, therefore, recommend that these disease models be assessed carefully as distinct entities to determine the implications of their experimental and clinical use.
脂多糖(LPS)和组织因子(TF)常用于诱导实验动物弥散性血管内凝血(DIC)模型。我们之前曾报道过,DIC 的病理生理学因诱导剂而异。然而,两种形式的 DIC 大鼠模型之间的炎症状态和出血症状尚未得到充分比较。除了肾脏的一些止血参数和病理发现外,我们还试图评估 LPS 和 TF 诱导的 DIC 模型的详细特征,特别是在炎症状态和出血症状方面。基于凝血酶-抗凝血酶复合物水平的结果,两种类型的实验性 DIC 的止血激活程度相同。在给予 LPS 时,观察到严重的器官功能障碍和肾脏中明显的纤维蛋白沉积,导致肿瘤坏死因子、白细胞介素-6 和高迁移率族蛋白 B1 浓度显著升高,而在给予 TF 时,D-二聚体浓度和出血症状显著升高。在 LPS 和 TF 诱导的 DIC 大鼠模型中,纤维蛋白溶解活性、器官功能障碍、炎症状态和出血症状的病理生理学有明显差异。因此,我们建议将这些疾病模型作为不同的实体进行仔细评估,以确定它们在实验和临床应用中的意义。