Abstract
BACKGROUND: Batroxobin is a thrombin-like enzyme derived from snake venom that exhibits not only antithrombotic effects due to its fibrinogen-degrading effects, but also inflammatory and tissue-protective effects by inhibiting neutrophil extracellular traps (NETs). This study aimed to investigate the effects of batroxobin on NET suppression and flap necrosis reduction in a rat island flap ischemia-reperfusion injury (IRI) model. METHODS: An island flap was created on the abdominal wall of a rat. The vascular pedicle was clamped for 6 hours and then released to establish the IRI model. Batroxobin (10 BU/kg) was administered intraperitoneally at the time of clamp release in the experimental group, whereas the control group received normal saline. The extent of blood perfusion within the flap was assessed using laser Doppler imaging, and NET expression was evaluated via S100A9 staining. RESULTS: Laser Doppler imaging exhibited the accelerated reperfusion area in batroxobin-treated rats compared with controls; 7 days postreperfusion, the rate of recovered area was 78.1% in the batroxobin group versus 44.6% in the control group. Histological analysis at 48 hours postreperfusion by S100A9 staining showed significantly reduced NETs in the batroxobin group; the S100A9-positive cells were 199.4 ± 63.7 per low power field in the batroxobin group versus 352.0 ± 76.4 per low power field in the control group. These findings indicate that batroxobin effectively preserved blood perfusion with a protective effect against tissue injury in the flap IRI model. CONCLUSIONS: These findings suggest that batroxobin may serve as a promising therapeutic agent for mitigating inflammatory tissue damage caused by IRI.