Deinagkistrodon acutus Venom Promotes Apoptosis of Vascular Tissue Cells Through PAR1, Leading To Mesenteric Vascular Damage

The Deinagkistrodon acutus is the most widely distributed venomous snake in China, and its clinical manifestations are primarily characterized by hemorrhage and coagulation disorders. Previous studies have suggested that mesenteric vascular injury induced by Deinagkistrodon acutus venom may be the primary cause of hemorrhage in envenomation. Protease-activated receptor 1 (PAR1) is highly expressed in vascular tissues and plays an important role in regulating the structure and function of blood vessels. This study aims to investigate the effects of Deinagkistrodon acutus venom on mesenteric vascular injury and to further explore the mechanisms underlying this injury, providing potential new therapeutic targets for clinical treatment. Seventy-two SD rats were randomly divided into three groups: Deinagkistrodon acutus venom intoxication group, inhibitor intervention group, and blank control group. Acute intoxication was induced by intraperitoneal injection of Deinagkistrodon acutus venom. The rats were observed at 3, 6, 12, and 24 h post-intoxication for abdominal hemorrhage, vascular structural changes, coagulation function, and platelet count to evaluate the success of the model. TUNEL assay, immunohistochemistry, and RT-qPCR were used to study the effects and mechanisms of Deinagkistrodon acutus venom in promoting mesenteric vascular injury. An acute intoxication model of Deinagkistrodon acutus venom was successfully established in rats. The venom promoted mesenteric vascular injury, and its mechanism may involve the downregulation of Bcl-2/Bax via PAR1, leading to the promotion of apoptosis of vascular tissue cells. Deinagkistrodon acutus venom induces mesenteric vascular injury through the PAR1-mediated downregulation of Bcl-2/Bax, promoting apoptosis of vascular tissue cells.