Management Department of Biosafety and Laboratory Animal, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan.
Toxins (Basel). 2021 Feb 18;13(2):160. doi: 10.3390/toxins13020160.
Disseminated intravascular coagulation, a severe clinical condition caused by an underlying disease, involves a markedly continuous and widespread activation of coagulation in the circulating blood and the formation of numerous microvascular thrombi. A snakebite, including that of the Yamakagashi (), demonstrates this clinical condition. Thus, an animal model using Yamakagashi venom was constructed. Yamakagashi venom was administered to rats, and its lethality and the changes in blood coagulation factors were detected after venom injection. When 300 μg venom was intramuscularly administered to 12-week-old rats, (1) they exhibited hematuria with plasma hemolysis and died within 48 h; (2) Thrombocytopenia in the blood was observed in the rats; (3) irreversible prolongation of prothrombin time in the plasma to the measurement limit occurred; (4) fibrinogen concentration in the plasma irreversibly decreased below the measurement limit; and (5) A transient increase in the plasma concentration of D-dimer was observed. In this model, a fixed amount of venom injection resulted in the clinical symptom similar to the human pathology with snakebite. The use of the rat model is very effective in validating the therapeutic effect of human disseminated intravascular coagulation condition due to snakebite.
弥散性血管内凝血,一种由潜在疾病引起的严重临床病症,涉及到循环血液中明显持续和广泛的凝血激活以及大量微血管血栓的形成。蛇咬伤,包括山颪蛇(Yamakagashi)的咬伤,就展示了这种临床病症。因此,构建了一种使用山颪蛇毒液的动物模型。向大鼠注射山颪蛇毒液,并在注射毒液后检测其致死率和凝血因子的变化。当 300μg 毒液被肌肉注射到 12 周龄大鼠中时,(1)它们表现出血尿伴血浆溶血,并在 48 小时内死亡;(2)血液中观察到血小板减少;(3)血浆中凝血酶原时间不可逆转地延长至测量极限;(4)血浆中纤维蛋白原浓度不可逆转地降至测量极限以下;以及(5)观察到血浆中 D-二聚体浓度的短暂升高。在该模型中,固定剂量的 毒液注射导致类似于人类蛇咬伤病理的临床症状。由于蛇咬伤导致的人类弥散性血管内凝血病症的治疗效果,该大鼠模型的使用非常有效。