Mesh : Animals Reperfusion Injury / prevention & control etiology Botulinum Toxins, Type A / pharmacology administration & dosage Rats, Sprague-Dawley NADPH Oxidases / metabolism antagonists & inhibitors Rats Male Reactive Oxygen Species / metabolism Surgical Flaps / blood supply Superoxides / metabolism Disease Models, Animal

来  源:   DOI:10.1097/PRS.0000000000010956

Abstract:
BACKGROUND: Despite the increasing popularity of various materials for ischemia-reperfusion (I/R) injury mitigation, research on botulinum toxin type A (BoNTA) remains limited. This study assesses BoNTA\'s efficacy in protecting flaps from I/R injury by inhibiting the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system and reducing reactive oxygen species (ROS) production.
METHODS: Seventy-six Sprague-Dawley rats were studied. We examined the effects of BoNTA on superoxide production in four rats using a lucigenin-enhanced chemiluminescence assay (LECL). Another group of 60 rats had their superficial inferior epigastric artery (SIEA) flaps treated with either BoNTA or saline and clamped for 0, 1, and 4 hours before reperfusion. Flap survival and histological outcomes were assessed five days post-operation. ROS production in SIEA flaps and femoral vessels was analyzed in 12 additional rats, post-I/R injury.
RESULTS: The LECL results showed that the BoNTA group had significantly lower superoxide production compared to controls, with notable reductions at 4 hours. While no significant differences were noted at the 0 and 1-hour marks, the 4-hour mark showed significant protective effects in BoNTA-treated groups. The survival rate was 90% for BoNTA-treated rats versus 60% for controls ( P = 0.028). Significant reductions in ROS were also observed in the 4-hour I/R group.
CONCLUSIONS: BoNTA effectively protects against I/R injury by inhibiting the NADPH oxidase system and reducing ROS levels. These results support further investigation into the specific mechanisms of NADPH oxidase inhibition by BoNTA and its potential clinical applications, given its safety profile.
CONCLUSIONS: The findings from the present study are expected to provide a basis for clinical studies regarding this use of BoNTA.
摘要:
背景:尽管用于减轻缺血再灌注(I/R)损伤的各种材料越来越受欢迎,对A型肉毒杆菌毒素(BoNTA)的研究仍然有限。这项研究评估了BoNTA通过抑制烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶系统和减少活性氧(ROS)产生来保护皮瓣免受I/R损伤的功效。
方法:研究了76只Sprague-Dawley大鼠。我们使用荧光素增强化学发光测定法(LECL)检查了BoNTA对四只大鼠超氧化物产生的影响。另一组60只大鼠的上腹下浅动脉(SIEA)皮瓣用BoNTA或盐水处理,并在再灌注前夹住0、1和4小时。术后五天评估皮瓣存活率和组织学结果。在另外12只大鼠中分析了SIEA皮瓣和股血管中的ROS产生,I/R后损伤。
结果:LECL结果显示,与对照组相比,BoNTA组的超氧化物产生显着降低,在4小时时显著减少。虽然在0和1小时标记处没有发现显着差异,4小时标记在BoNTA治疗组中显示出显著的保护作用。BoNTA处理的大鼠的存活率为90%,而对照组为60%(P=0.028)。在4小时I/R组中还观察到ROS的显著减少。
结论:BoNTA通过抑制NADPH氧化酶系统和降低ROS水平有效保护I/R损伤。这些结果支持进一步研究BoNTA抑制NADPH氧化酶的具体机制及其潜在的临床应用。鉴于其安全性。
结论:本研究的发现有望为有关BoNTA使用的临床研究提供基础。
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