Department of Emergency Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Lishui Hospital of Zhejiang University, Lishui, China.
Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Toxicon. 2024 Apr;241:107683. doi: 10.1016/j.toxicon.2024.107683. Epub 2024 Mar 7.
To establish a preclinical large-animal model of Deinagkistrodon acutus snakebite envenomation and evaluate its feasibility.
The venom of D. acutus (0 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, or 10 mg/kg) was injected into the left biceps femoris of 11 male pigs. Then, the circumferences of the limbs were regularly measured, and changes in muscle injury biomarkers, blood parameters, coagulation function, vital organ function and injury biomarkers were regularly detected. At 24 h after venom injection, the animals were euthanized, and the pathological damage to the vital organs mentioned above was evaluated.
The two pigs receiving 10 mg/kg and 5 mg/kg snake venom died at 8 h and 12 h after injection, respectively. The remaining pigs were equally divided into 0 mg/kg, 1 mg/kg, and 2 mg/kg snake venom groups, and all of them survived to 24 h after injection. Compared with the pigs receiving 0 mg/kg snake venom, the pigs receiving 1 mg/kg or 2 mg/kg snake venom exhibited significant abnormities, including limb swelling; increased muscle injury biomarker creatine kinase (CK) and coagulation function indicators prothrombin time and D-dimer; and decreased blood routine indicator platelet and coagulation function indicator fibrinogen. Moreover, significant abnormalities in myocardial and cerebral function and injury biomarkers in the heart, brain, liver, kidney and intestine were also observed. In particular, the abnormalities mentioned above were significantly obvious in those pigs receiving 2 mg/kg snake venom. Pathological evaluation revealed that the morphology of muscle, heart, brain, liver, kidney, and intestine in those pigs receiving 0 mg/kg snake venom was normal; however, pathological damage was observed in those pigs receiving 1 mg/kg and 2 mg/kg snake venom. Similarly, the pathological damage was more severe in those pigs receiving 2 mg/kg snake venom.
The intramuscular injection of 2 mg/kg D. acutus venom seems to be an optimal dose for examining the preclinical efficacy of existing and novel therapeutics for treating D. acutus envenomation in pigs.
建立尖吻蝮蛇咬伤的临床前大型动物模型，并评估其可行性。
将尖吻蝮蛇毒液（0mg/kg、1mg/kg、2mg/kg、5mg/kg 或 10mg/kg）注入 11 头雄性猪的左股二头肌。然后定期测量四肢的周长，并定期检测肌肉损伤生物标志物、血液参数、凝血功能、重要器官功能和损伤生物标志物的变化。在毒液注射后 24 小时，处死动物，评估上述重要器官的病理损伤。
注射 10mg/kg 和 5mg/kg 蛇毒的 2 头猪分别在注射后 8 小时和 12 小时死亡。其余猪等分为 0mg/kg、1mg/kg 和 2mg/kg 蛇毒组，所有猪均存活至注射后 24 小时。与注射 0mg/kg 蛇毒的猪相比，注射 1mg/kg 或 2mg/kg 蛇毒的猪表现出明显的异常，包括四肢肿胀；肌肉损伤生物标志物肌酸激酶（CK）和凝血功能指标凝血酶原时间和 D-二聚体增加；血常规指标血小板和凝血功能指标纤维蛋白原减少。此外，还观察到心脏、大脑、肝脏、肾脏和肠道的心肌和脑功能以及损伤生物标志物明显异常。特别是注射 2mg/kg 蛇毒的猪异常更为明显。病理评估显示，注射 0mg/kg 蛇毒的猪肌肉、心脏、大脑、肝脏、肾脏和肠道的形态正常；然而，注射 1mg/kg 和 2mg/kg 蛇毒的猪则观察到病理损伤。同样，注射 2mg/kg 蛇毒的猪的病理损伤更为严重。
肌肉内注射 2mg/kg 尖吻蝮蛇毒液似乎是检查现有和新型治疗方法治疗猪尖吻蝮蛇咬伤的临床前疗效的最佳剂量。
